Nutrient chapter

Chloride

Chloride nutrient topic. The independently modeled chemical species is chloride ion (Cl−). Dietary shortage, gastrointestinal or renal losses, blood concentration, intracellular gradients and genetic transport defects are different states. Sodium chloride, potassium chloride and chloride-rich intravenous fluids retain their accompanying ions and routes.

86 recorded mechanisms · 14 availability situations · 5 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Chloride bound the WNK1 catalytic region and stabilized its inactive conformation.
Chloride ion → Human WNK lysine deficient protein kinase 1 / WNK1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"}
experimental_model
Crystallography and kinase mutagenesis
exposure
Chloride binding and chloride-pocket mutants
limitations
Cell-free sensing; plasma chloride is not identical to kinase-site chloride.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human WNK1 kinase constructs
plain_language
Chloride can act as a direct signal to a kinase, not just as an accompanying ion.
primary_references
[chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050
tissue_or_cell_type
Purified kinase domain
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 315–326
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography and kinase mutagenesis · source_derived_draft · unverified_draft
### chloride-wnk1-binding Chloride bound the WNK1 catalytic region and stabilized its inactive conformation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride can act as a direct signal to a kinase, not just as an accompanying ion. organism: Human WNK1 kinase constructs tissue_or_cell_type: Purified kinase domain experimental_model: Crystallography and kinase mutagenesis limitations: Cell-free sensing; plasma chloride is not identical to kinase-site chloride. exposure: Chloride binding and chloride-pocket mutants evidence_span: {"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"} [chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050
Complete structured claim and evidence
Chloride inhibited WNK1 autophosphorylation; binding-site mutations reduced this inhibition.
Chloride ion → Human WNK lysine deficient protein kinase 1 / WNK1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"}
experimental_model
Crystallography and kinase mutagenesis
exposure
Chloride binding and chloride-pocket mutants
limitations
Cell-free sensing; plasma chloride is not identical to kinase-site chloride.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human WNK1 kinase constructs
plain_language
When the chloride brake is released, this kinase can activate itself.
primary_references
[chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050
tissue_or_cell_type
Purified kinase domain
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 328–339
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography and kinase mutagenesis · source_derived_draft · unverified_draft
### chloride-wnk1-inhibition Chloride inhibited WNK1 autophosphorylation; binding-site mutations reduced this inhibition. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: When the chloride brake is released, this kinase can activate itself. organism: Human WNK1 kinase constructs tissue_or_cell_type: Purified kinase domain experimental_model: Crystallography and kinase mutagenesis limitations: Cell-free sensing; plasma chloride is not identical to kinase-site chloride. exposure: Chloride binding and chloride-pocket mutants evidence_span: {"source_cache": "artifacts/chloride-research/24803536.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb", "start_char": 0, "end_char": 1200, "text_sha256": "77c3ca2b36fc42c41bf361696bca69b3c185442ff3ef389055a95f4615dda6cb"} [chloride-p24803536] Chloride sensing by WNK1 involves inhibition of autophosphorylation. (2014). https://pubmed.ncbi.nlm.nih.gov/24803536/ DOI: 10.1126/scisignal.2005050
Complete structured claim and evidence
Phosphorylated CFTR channels opened with ATP but not Mg-free ATP in this preparation.
Magnesium-ATP complex → CFTR anion conductance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/1718606.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67", "start_char": 0, "end_char": 925, "text_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67"}
experimental_model
Phosphorylated CFTR channel nucleotide assays
exposure
Hydrolyzable nucleotides, analogues and Mg-free ATP
limitations
Records the measured Mg/nucleotide dependence, not the paper’s historical assignment of opening to NBD1 hydrolysis.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human CFTR in expression preparations
plain_language
Magnesium and ATP are part of the working channel system; chloride alone is insufficient.
primary_references
[chloride-p1718606] Nucleoside triphosphates are required to open the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1718606/ DOI: 10.1016/0092-8674(91)90072-7
tissue_or_cell_type
Cytosolic channel face
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 250–261
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphorylated CFTR channel nucleotide assays · source_derived_draft · unverified_draft
### chloride-cftr-mgatp Phosphorylated CFTR channels opened with ATP but not Mg-free ATP in this preparation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium and ATP are part of the working channel system; chloride alone is insufficient. organism: Human CFTR in expression preparations tissue_or_cell_type: Cytosolic channel face experimental_model: Phosphorylated CFTR channel nucleotide assays limitations: Records the measured Mg/nucleotide dependence, not the paper’s historical assignment of opening to NBD1 hydrolysis. exposure: Hydrolyzable nucleotides, analogues and Mg-free ATP evidence_span: {"source_cache": "artifacts/chloride-research/1718606.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67", "start_char": 0, "end_char": 925, "text_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67"} [chloride-p1718606] Nucleoside triphosphates are required to open the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1718606/ DOI: 10.1016/0092-8674(91)90072-7
Complete structured claim and evidence
Pendrin-null collecting ducts had reduced apical chloride/bicarbonate exchange and impaired bicarbonate secretion.
Mouse pendrin / Slc26a4 → Renal bicarbonate secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/20375274.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953", "start_char": 0, "end_char": 1797, "text_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953"}
experimental_model
Pendrin knockout and isolated collecting-duct perfusion
exposure
Slc26a4 deletion
limitations
Residual exchange remained; baseline urine chloride excretion was unchanged.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
The kidney uses chloride exchange to help dispose of bicarbonate.
primary_references
[chloride-p20375274] Deletion of the anion exchanger Slc26a4 (pendrin) decreases apical Cl(-)/HCO3(-) exchanger activity and impairs bicarbonate secretion in kidney collecting duct. (2010). https://pubmed.ncbi.nlm.nih.gov/20375274/ DOI: 10.1152/ajpcell.00033.2010
tissue_or_cell_type
Non-acid-secreting intercalated cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 510–521
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pendrin knockout and isolated collecting-duct perfusion · source_derived_draft · unverified_draft
### chloride-pendrin-bicarbonate Pendrin-null collecting ducts had reduced apical chloride/bicarbonate exchange and impaired bicarbonate secretion. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney uses chloride exchange to help dispose of bicarbonate. organism: Mouse tissue_or_cell_type: Non-acid-secreting intercalated cells experimental_model: Pendrin knockout and isolated collecting-duct perfusion limitations: Residual exchange remained; baseline urine chloride excretion was unchanged. exposure: Slc26a4 deletion evidence_span: {"source_cache": "artifacts/chloride-research/20375274.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953", "start_char": 0, "end_char": 1797, "text_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953"} [chloride-p20375274] Deletion of the anion exchanger Slc26a4 (pendrin) decreases apical Cl(-)/HCO3(-) exchanger activity and impairs bicarbonate secretion in kidney collecting duct. (2010). https://pubmed.ncbi.nlm.nih.gov/20375274/ DOI: 10.1152/ajpcell.00033.2010
Complete structured claim and evidence
Oral KCl corrected induced chloride-depletion alkalosis while plasma volume, body weight and filtration remained reduced.
Potassium chloride → Chloride-depletion metabolic alkalosis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/2450456.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7", "start_char": 0, "end_char": 1348, "text_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7"}
experimental_model
Human depletion–repletion balance experiment
exposure
Furosemide plus restricted NaCl; oral KCl repletion over 36 hours
limitations
Loss-associated depletion; KCl supplies potassium too. Mechanism does not imply self-treatment or apply to every alkalosis.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human men
plain_language
Restoring volume was not necessary for correction in this experiment.
primary_references
[chloride-p2450456] On the mechanism by which chloride corrects metabolic alkalosis in man. (1988). https://pubmed.ncbi.nlm.nih.gov/2450456/ DOI: 10.1016/0002-9343(88)90265-3
tissue_or_cell_type
Kidney and systemic acid–base balance
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 835–846
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human depletion–repletion balance experiment · source_derived_draft · unverified_draft
### chloride-repletion-alkalosis Oral KCl corrected induced chloride-depletion alkalosis while plasma volume, body weight and filtration remained reduced. Condition category: nutrient_deficiency nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring volume was not necessary for correction in this experiment. organism: Human men tissue_or_cell_type: Kidney and systemic acid–base balance experimental_model: Human depletion–repletion balance experiment limitations: Loss-associated depletion; KCl supplies potassium too. Mechanism does not imply self-treatment or apply to every alkalosis. exposure: Furosemide plus restricted NaCl; oral KCl repletion over 36 hours evidence_span: {"source_cache": "artifacts/chloride-research/2450456.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7", "start_char": 0, "end_char": 1348, "text_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7"} [chloride-p2450456] On the mechanism by which chloride corrects metabolic alkalosis in man. (1988). https://pubmed.ncbi.nlm.nih.gov/2450456/ DOI: 10.1016/0002-9343(88)90265-3
Complete structured claim and evidence
Chloride binding increased catalytic rates and altered pH dependence of the human pancreatic amylase variant.
Chloride ion → Pancreatic alpha-amylase catalytic activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/15722449.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82", "start_char": 0, "end_char": 1748, "text_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82"}
experimental_model
Structure and kinetics
exposure
N298S variant with and without chloride
limitations
Variant-focused structural mechanism; not a clinical maldigestion threshold.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human pancreatic alpha-amylase variant
plain_language
Chloride directly helps a starch-digesting enzyme function.
primary_references
[chloride-p15722449] Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase. (2005). https://pubmed.ncbi.nlm.nih.gov/15722449/ DOI: 10.1110/ps.041079305
tissue_or_cell_type
Purified digestive enzyme
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 588–599
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Structure and kinetics · source_derived_draft · unverified_draft
### chloride-amylase-activation Chloride binding increased catalytic rates and altered pH dependence of the human pancreatic amylase variant. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride directly helps a starch-digesting enzyme function. organism: Human pancreatic alpha-amylase variant tissue_or_cell_type: Purified digestive enzyme experimental_model: Structure and kinetics limitations: Variant-focused structural mechanism; not a clinical maldigestion threshold. exposure: N298S variant with and without chloride evidence_span: {"source_cache": "artifacts/chloride-research/15722449.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82", "start_char": 0, "end_char": 1748, "text_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82"} [chloride-p15722449] Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase. (2005). https://pubmed.ncbi.nlm.nih.gov/15722449/ DOI: 10.1110/ps.041079305
Complete structured claim and evidence
The Clcn5-null model lost 25-hydroxyvitamin D3 in urine.
Mouse ClC-5 chloride/proton exchanger / Clcn5 → Urinary loss of 25-hydroxyvitamin D3 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"}
experimental_model
Clcn5 knockout and uptake measurements
exposure
Clcn5 disruption
limitations
The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
The transporter defect connects chloride machinery to vitamin D handling.
primary_references
[chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597
tissue_or_cell_type
Proximal renal tubule
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 692–703
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn5 knockout and uptake measurements · source_derived_draft · unverified_draft
### chloride-clc5-vitd-loss The Clcn5-null model lost 25-hydroxyvitamin D3 in urine. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transporter defect connects chloride machinery to vitamin D handling. organism: Mouse tissue_or_cell_type: Proximal renal tubule experimental_model: Clcn5 knockout and uptake measurements limitations: The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated. exposure: Clcn5 disruption evidence_span: {"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"} [chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597
Complete structured claim and evidence
Developmental KCC2 expression accompanied the shift toward hyperpolarizing GABA-A responses.
Rat potassium/chloride cotransporter KCC2 / Slc12a5 → Chloride ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"}
experimental_model
Developmental expression and antisense suppression
exposure
KCC2 expression during maturation; antisense inhibition
limitations
Neuronal gradient mechanism; dietary chloride restriction is not the intervention.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Rat
plain_language
Potassium-coupled chloride removal helps mature neurons respond to GABA with inhibition.
primary_references
[chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697
tissue_or_cell_type
Hippocampal pyramidal neurons
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 393–404
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Developmental expression and antisense suppression · source_derived_draft · unverified_draft
### chloride-kcc2-cl-extrusion Developmental KCC2 expression accompanied the shift toward hyperpolarizing GABA-A responses. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium-coupled chloride removal helps mature neurons respond to GABA with inhibition. organism: Rat tissue_or_cell_type: Hippocampal pyramidal neurons experimental_model: Developmental expression and antisense suppression limitations: Neuronal gradient mechanism; dietary chloride restriction is not the intervention. exposure: KCC2 expression during maturation; antisense inhibition evidence_span: {"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"} [chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697
Complete structured claim and evidence
Clcn7-null osteoclasts failed to acidify the resorption lacuna.
Mouse ClC-7 chloride/proton exchanger / Clcn7 → Acidification of the osteoclast resorption lacuna source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/11207362.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a", "start_char": 0, "end_char": 821, "text_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a"}
experimental_model
Clcn7 knockout and human mutation identification
exposure
ClC-7 loss
limitations
Historical title calls ClC-7 a channel; current exchanger classification does not change the reported knockout phenotype. Not a dietary chloride study.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse; human infantile osteopetrosis patient
plain_language
Chloride-handling machinery supports the acidic compartment used to resorb bone.
primary_references
[chloride-p11207362] Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. (2001). https://pubmed.ncbi.nlm.nih.gov/11207362/ DOI: 10.1016/s0092-8674(01)00206-9
tissue_or_cell_type
Osteoclast ruffled border
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 770–781
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn7 knockout and human mutation identification · source_derived_draft · unverified_draft
### chloride-clc7-acidification Clcn7-null osteoclasts failed to acidify the resorption lacuna. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride-handling machinery supports the acidic compartment used to resorb bone. organism: Mouse; human infantile osteopetrosis patient tissue_or_cell_type: Osteoclast ruffled border experimental_model: Clcn7 knockout and human mutation identification limitations: Historical title calls ClC-7 a channel; current exchanger classification does not change the reported knockout phenotype. Not a dietary chloride study. exposure: ClC-7 loss evidence_span: {"source_cache": "artifacts/chloride-research/11207362.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a", "start_char": 0, "end_char": 821, "text_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a"} [chloride-p11207362] Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. (2001). https://pubmed.ncbi.nlm.nih.gov/11207362/ DOI: 10.1016/s0092-8674(01)00206-9
Complete structured claim and evidence
Myeloperoxidase used hydrogen peroxide to oxidize chloride to hypochlorous acid.
Human myeloperoxidase / MPO → Hypochlorous acid / HOCl source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/9359420.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0", "start_char": 0, "end_char": 1700, "text_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0"}
experimental_model
Purified-enzyme substrate kinetics
exposure
100 mM chloride with varying thiocyanate
limitations
Product chemistry under assay conditions; not a recommendation to raise chloride or thiocyanate intake.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human neutrophil enzyme
plain_language
Immune chemistry can convert chloride into a reactive antimicrobial oxidant.
primary_references
[chloride-p9359420] Thiocyanate and chloride as competing substrates for myeloperoxidase. (1997). https://pubmed.ncbi.nlm.nih.gov/9359420/ DOI: 10.1042/bj3270487
tissue_or_cell_type
Myeloperoxidase reaction mixture
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 614–625
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme substrate kinetics · source_derived_draft · unverified_draft
### chloride-mpo-hocl Myeloperoxidase used hydrogen peroxide to oxidize chloride to hypochlorous acid. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Immune chemistry can convert chloride into a reactive antimicrobial oxidant. organism: Human neutrophil enzyme tissue_or_cell_type: Myeloperoxidase reaction mixture experimental_model: Purified-enzyme substrate kinetics limitations: Product chemistry under assay conditions; not a recommendation to raise chloride or thiocyanate intake. exposure: 100 mM chloride with varying thiocyanate evidence_span: {"source_cache": "artifacts/chloride-research/9359420.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0", "start_char": 0, "end_char": 1700, "text_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0"} [chloride-p9359420] Thiocyanate and chloride as competing substrates for myeloperoxidase. (1997). https://pubmed.ncbi.nlm.nih.gov/9359420/ DOI: 10.1042/bj3270487
Complete structured claim and evidence
A seven-month-old infant fed chloride-deficient formula developed hypochloremic alkalosis.
Chloride → Chloride-depletion metabolic alkalosis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/7293908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4d85273187d5fba7fc6f5c38bda3da041dc4751715a0e65c995ba6898650a84", "start_char": 0, "end_char": 458, "text_sha256": "a4d85273187d5fba7fc6f5c38bda3da041dc4751715a0e65c995ba6898650a84"}
experimental_model
Infant case and formula correction
exposure
Chloride-deficient formula replaced with adequate formula
limitations
Uncontrolled historical case; formula replacement is not a universal dose-response experiment.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human
plain_language
A true dietary shortage was documented under this unusual feeding condition.
primary_references
[chloride-p7293908] Metabolic effects of chloride-deficient formula. (1981). https://pubmed.ncbi.nlm.nih.gov/7293908/
tissue_or_cell_type
Diet, growth and blood chemistry
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 796–807
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Infant case and formula correction · source_derived_draft · unverified_draft
### chloride-formula-alkalosis A seven-month-old infant fed chloride-deficient formula developed hypochloremic alkalosis. Condition category: nutrient_deficiency nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A true dietary shortage was documented under this unusual feeding condition. organism: Human tissue_or_cell_type: Diet, growth and blood chemistry experimental_model: Infant case and formula correction limitations: Uncontrolled historical case; formula replacement is not a universal dose-response experiment. exposure: Chloride-deficient formula replaced with adequate formula evidence_span: {"source_cache": "artifacts/chloride-research/7293908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4d85273187d5fba7fc6f5c38bda3da041dc4751715a0e65c995ba6898650a84", "start_char": 0, "end_char": 458, "text_sha256": "a4d85273187d5fba7fc6f5c38bda3da041dc4751715a0e65c995ba6898650a84"} [chloride-p7293908] Metabolic effects of chloride-deficient formula. (1981). https://pubmed.ncbi.nlm.nih.gov/7293908/
Complete structured claim and evidence
Saline produced sustained hyperchloremia, unlike Plasma-Lyte 148.
0.9% sodium chloride intravenous solution → Plasma or serum chloride concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/22580944.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814", "start_char": 0, "end_char": 1757, "text_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814"}
experimental_model
Randomized blinded crossover
exposure
2 L saline or Plasma-Lyte 148 over one hour
limitations
IV fluid formulations differ in several components; short-term perfusion is not kidney failure or dietary salt exposure.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Twelve healthy adult men
plain_language
The chloride content of a large IV fluid load changes blood chemistry.
primary_references
[chloride-p22580944] A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. (2012). https://pubmed.ncbi.nlm.nih.gov/22580944/ DOI: 10.1097/sla.0b013e318256be72
tissue_or_cell_type
Renal MRI and blood chemistry
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 965–976
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized blinded crossover · source_derived_draft · unverified_draft
### chloride-saline-chloride Saline produced sustained hyperchloremia, unlike Plasma-Lyte 148. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chloride content of a large IV fluid load changes blood chemistry. organism: Twelve healthy adult men tissue_or_cell_type: Renal MRI and blood chemistry experimental_model: Randomized blinded crossover limitations: IV fluid formulations differ in several components; short-term perfusion is not kidney failure or dietary salt exposure. exposure: 2 L saline or Plasma-Lyte 148 over one hour evidence_span: {"source_cache": "artifacts/chloride-research/22580944.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814", "start_char": 0, "end_char": 1757, "text_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814"} [chloride-p22580944] A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. (2012). https://pubmed.ncbi.nlm.nih.gov/22580944/ DOI: 10.1097/sla.0b013e318256be72
Complete structured claim and evidence
DRA variants segregated with congenital chloride diarrhea in the studied families.
Human intestinal chloride/bicarbonate exchanger DRA / SLC26A3 → Intestinal chloride loss source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/8896562.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7883032c511e388e8c37bf64651bb2e9b19ef65fee624c0e8c31359894fe9e64", "start_char": 0, "end_char": 1272, "text_sha256": "7883032c511e388e8c37bf64651bb2e9b19ef65fee624c0e8c31359894fe9e64"}
experimental_model
Genetic mapping in 32 Finnish and four Polish patients
exposure
Inherited DRA variants
limitations
Human transport disease; does not imply low dietary intake or a dietary cure.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human
plain_language
A defective intestinal exchanger can cause chloride-rich diarrhea even when chloride is consumed.
primary_references
[chloride-p8896562] Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea. (1996). https://pubmed.ncbi.nlm.nih.gov/8896562/ DOI: 10.1038/ng1196-316
tissue_or_cell_type
Intestinal epithelium
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 159–170
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic mapping in 32 Finnish and four Polish patients · source_derived_draft · unverified_draft
### chloride-dra-loss DRA variants segregated with congenital chloride diarrhea in the studied families. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defective intestinal exchanger can cause chloride-rich diarrhea even when chloride is consumed. organism: Human tissue_or_cell_type: Intestinal epithelium experimental_model: Genetic mapping in 32 Finnish and four Polish patients limitations: Human transport disease; does not imply low dietary intake or a dietary cure. exposure: Inherited DRA variants evidence_span: {"source_cache": "artifacts/chloride-research/8896562.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7883032c511e388e8c37bf64651bb2e9b19ef65fee624c0e8c31359894fe9e64", "start_char": 0, "end_char": 1272, "text_sha256": "7883032c511e388e8c37bf64651bb2e9b19ef65fee624c0e8c31359894fe9e64"} [chloride-p8896562] Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea. (1996). https://pubmed.ncbi.nlm.nih.gov/8896562/ DOI: 10.1038/ng1196-316
Complete structured claim and evidence
AE2-null mice failed to secrete gastric acid.
Mouse anion exchanger 2 / Slc4a2 → Gastric acid secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/15123620.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab", "start_char": 0, "end_char": 1416, "text_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab"}
experimental_model
Targeted Slc4a2 deletion
exposure
AE2-null versus control mice
limitations
Whole-gene loss affects membrane development as well as transport; not dietary chloride depletion.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
Stomach acid production requires functioning chloride-handling machinery.
primary_references
[chloride-p15123620] Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric. (2004). https://pubmed.ncbi.nlm.nih.gov/15123620/ DOI: 10.1074/jbc.m403779200
tissue_or_cell_type
Gastric parietal cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 172–183
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted Slc4a2 deletion · source_derived_draft · unverified_draft
### chloride-ae2-acid AE2-null mice failed to secrete gastric acid. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Stomach acid production requires functioning chloride-handling machinery. organism: Mouse tissue_or_cell_type: Gastric parietal cells experimental_model: Targeted Slc4a2 deletion limitations: Whole-gene loss affects membrane development as well as transport; not dietary chloride depletion. exposure: AE2-null versus control mice evidence_span: {"source_cache": "artifacts/chloride-research/15123620.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab", "start_char": 0, "end_char": 1416, "text_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab"} [chloride-p15123620] Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric. (2004). https://pubmed.ncbi.nlm.nih.gov/15123620/ DOI: 10.1074/jbc.m403779200
Complete structured claim and evidence
AE2-null parietal cells had poorly developed secretory canaliculi and few tubulovesicles.
Mouse anion exchanger 2 / Slc4a2 → Gastric parietal-cell secretory membrane organization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/15123620.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab", "start_char": 0, "end_char": 1416, "text_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab"}
experimental_model
Targeted Slc4a2 deletion
exposure
AE2-null versus control mice
limitations
Whole-gene loss affects membrane development as well as transport; not dietary chloride depletion.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
Removing the exchanger also changed the cell structures used for secretion.
primary_references
[chloride-p15123620] Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric. (2004). https://pubmed.ncbi.nlm.nih.gov/15123620/ DOI: 10.1074/jbc.m403779200
tissue_or_cell_type
Gastric parietal cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 185–196
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted Slc4a2 deletion · source_derived_draft · unverified_draft
### chloride-ae2-membranes AE2-null parietal cells had poorly developed secretory canaliculi and few tubulovesicles. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the exchanger also changed the cell structures used for secretion. organism: Mouse tissue_or_cell_type: Gastric parietal cells experimental_model: Targeted Slc4a2 deletion limitations: Whole-gene loss affects membrane development as well as transport; not dietary chloride depletion. exposure: AE2-null versus control mice evidence_span: {"source_cache": "artifacts/chloride-research/15123620.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab", "start_char": 0, "end_char": 1416, "text_sha256": "e2625c35640cf2ef20c066d3b628a000b6d37756e1245624670c45bc247468ab"} [chloride-p15123620] Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric. (2004). https://pubmed.ncbi.nlm.nih.gov/15123620/ DOI: 10.1074/jbc.m403779200
Complete structured claim and evidence
Slc26a9-null mice lost gastric acid secretion at five weeks.
Mouse gastric anion transporter Slc26a9 → Gastric acid secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/19004773.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e", "start_char": 0, "end_char": 1342, "text_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e"}
experimental_model
Slc26a9 deletion and heterologous transport assays
exposure
Knockout at five weeks; expression assays
limitations
Different assays showed conductance or exchange; do not assign one universal stoichiometry.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse protein; oocytes and cultured cells
plain_language
A second chloride-handling protein is needed for normal acid secretion in this model.
primary_references
[chloride-p19004773] Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach. (2008). https://pubmed.ncbi.nlm.nih.gov/19004773/ DOI: 10.1073/pnas.0800616105
tissue_or_cell_type
Gastric parietal cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 198–209
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc26a9 deletion and heterologous transport assays · source_derived_draft · unverified_draft
### chloride-slc26a9-acid Slc26a9-null mice lost gastric acid secretion at five weeks. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second chloride-handling protein is needed for normal acid secretion in this model. organism: Mouse protein; oocytes and cultured cells tissue_or_cell_type: Gastric parietal cells experimental_model: Slc26a9 deletion and heterologous transport assays limitations: Different assays showed conductance or exchange; do not assign one universal stoichiometry. exposure: Knockout at five weeks; expression assays evidence_span: {"source_cache": "artifacts/chloride-research/19004773.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e", "start_char": 0, "end_char": 1342, "text_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e"} [chloride-p19004773] Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach. (2008). https://pubmed.ncbi.nlm.nih.gov/19004773/ DOI: 10.1073/pnas.0800616105
Complete structured claim and evidence
Slc26a9 deletion eliminated parietal-cell tubulovesicles and shifted H-K-ATPase localization to the apical pole.
Mouse gastric anion transporter Slc26a9 → Gastric parietal-cell secretory membrane organization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/19004773.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e", "start_char": 0, "end_char": 1342, "text_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e"}
experimental_model
Slc26a9 deletion and heterologous transport assays
exposure
Knockout at five weeks; expression assays
limitations
Different assays showed conductance or exchange; do not assign one universal stoichiometry.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse protein; oocytes and cultured cells
plain_language
The secretory machinery changed as well as the acid output.
primary_references
[chloride-p19004773] Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach. (2008). https://pubmed.ncbi.nlm.nih.gov/19004773/ DOI: 10.1073/pnas.0800616105
tissue_or_cell_type
Gastric parietal cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 211–222
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc26a9 deletion and heterologous transport assays · source_derived_draft · unverified_draft
### chloride-slc26a9-membranes Slc26a9 deletion eliminated parietal-cell tubulovesicles and shifted H-K-ATPase localization to the apical pole. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The secretory machinery changed as well as the acid output. organism: Mouse protein; oocytes and cultured cells tissue_or_cell_type: Gastric parietal cells experimental_model: Slc26a9 deletion and heterologous transport assays limitations: Different assays showed conductance or exchange; do not assign one universal stoichiometry. exposure: Knockout at five weeks; expression assays evidence_span: {"source_cache": "artifacts/chloride-research/19004773.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e", "start_char": 0, "end_char": 1342, "text_sha256": "ed1a2033c883ec9b4eeab6a9c0bae03d1f478adf66913c3d5e8c43879a836d3e"} [chloride-p19004773] Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach. (2008). https://pubmed.ncbi.nlm.nih.gov/19004773/ DOI: 10.1073/pnas.0800616105
Complete structured claim and evidence
CFTR pore-region mutations changed anion selectivity, demonstrating that CFTR forms an anion channel.
Human cystic fibrosis transmembrane conductance regulator / CFTR → Chloride ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/1712984.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b", "start_char": 0, "end_char": 849, "text_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b"}
experimental_model
CFTR expression and pore-residue mutagenesis
exposure
K95 or K335 substitutions
limitations
Selectivity experiment; not a supplementation study.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human CFTR in expression systems
plain_language
CFTR provides a route through which chloride can cross a membrane.
primary_references
[chloride-p1712984] Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. (1991). https://pubmed.ncbi.nlm.nih.gov/1712984/ DOI: 10.1126/science.1712984
tissue_or_cell_type
Cell plasma membrane
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 224–235
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CFTR expression and pore-residue mutagenesis · source_derived_draft · unverified_draft
### chloride-cftr-channel CFTR pore-region mutations changed anion selectivity, demonstrating that CFTR forms an anion channel. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: CFTR provides a route through which chloride can cross a membrane. organism: Human CFTR in expression systems tissue_or_cell_type: Cell plasma membrane experimental_model: CFTR expression and pore-residue mutagenesis limitations: Selectivity experiment; not a supplementation study. exposure: K95 or K335 substitutions evidence_span: {"source_cache": "artifacts/chloride-research/1712984.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b", "start_char": 0, "end_char": 849, "text_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b"} [chloride-p1712984] Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. (1991). https://pubmed.ncbi.nlm.nih.gov/1712984/ DOI: 10.1126/science.1712984
Complete structured claim and evidence
PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal.
Protein kinase A → Human cystic fibrosis transmembrane conductance regulator / CFTR source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/1716180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5", "start_char": 0, "end_char": 961, "text_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5"}
experimental_model
PKA phosphorylation and CFTR mutagenesis
exposure
Serines 660, 737, 795 and 813
limitations
Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human CFTR in cells
plain_language
A kinase switches the channel into a state that can respond to stimulation.
primary_references
[chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6
tissue_or_cell_type
CFTR regulatory domain
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 237–248
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PKA phosphorylation and CFTR mutagenesis · source_derived_draft · unverified_draft
### chloride-pka-cftr PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase switches the channel into a state that can respond to stimulation. organism: Human CFTR in cells tissue_or_cell_type: CFTR regulatory domain experimental_model: PKA phosphorylation and CFTR mutagenesis limitations: Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model. exposure: Serines 660, 737, 795 and 813 evidence_span: {"source_cache": "artifacts/chloride-research/1716180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5", "start_char": 0, "end_char": 961, "text_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5"} [chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6
Complete structured claim and evidence
Lower intracellular chloride activated the WNK1–OSR1/SPAK pathway in the pancreatic experiments.
Intracellular chloride concentration → Human WNK lysine deficient protein kinase 1 / WNK1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"}
experimental_model
Expression, duct-cell and pancreatic-tissue experiments
exposure
Low intracellular chloride; WNK1–OSR1/SPAK activation
limitations
Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human and guinea pig
plain_language
A fall in chloride inside a duct cell can switch its secretory program.
primary_references
[chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
tissue_or_cell_type
Pancreatic duct
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 263–274
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression, duct-cell and pancreatic-tissue experiments · source_derived_draft · unverified_draft
### chloride-pancreatic-cl-signal Lower intracellular chloride activated the WNK1–OSR1/SPAK pathway in the pancreatic experiments. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A fall in chloride inside a duct cell can switch its secretory program. organism: Human and guinea pig tissue_or_cell_type: Pancreatic duct experimental_model: Expression, duct-cell and pancreatic-tissue experiments limitations: Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency. exposure: Low intracellular chloride; WNK1–OSR1/SPAK activation evidence_span: {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"} [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
Complete structured claim and evidence
WNK1-mediated OSR1/SPAK activation increased CFTR bicarbonate permeability.
Human WNK lysine deficient protein kinase 1 / WNK1 → CFTR bicarbonate permeability source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"}
experimental_model
Expression, duct-cell and pancreatic-tissue experiments
exposure
Low intracellular chloride; WNK1–OSR1/SPAK activation
limitations
Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human and guinea pig
plain_language
The channel became better at carrying bicarbonate for alkaline pancreatic fluid.
primary_references
[chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
tissue_or_cell_type
Pancreatic duct
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 276–287
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression, duct-cell and pancreatic-tissue experiments · source_derived_draft · unverified_draft
### chloride-pancreatic-bicarbonate WNK1-mediated OSR1/SPAK activation increased CFTR bicarbonate permeability. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The channel became better at carrying bicarbonate for alkaline pancreatic fluid. organism: Human and guinea pig tissue_or_cell_type: Pancreatic duct experimental_model: Expression, duct-cell and pancreatic-tissue experiments limitations: Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency. exposure: Low intracellular chloride; WNK1–OSR1/SPAK activation evidence_span: {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"} [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
Complete structured claim and evidence
OSR1/SPAK activation inhibited CFTR-dependent chloride/bicarbonate exchange in the tested system.
Oxidative stress responsive kinase 1 → Pancreatic CFTR-dependent chloride/bicarbonate exchange activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"}
experimental_model
Expression, duct-cell and pancreatic-tissue experiments
exposure
Low intracellular chloride; WNK1–OSR1/SPAK activation
limitations
Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human and guinea pig
plain_language
The same signaling program reduced an exchange route that could take bicarbonate back from the secretion.
primary_references
[chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
tissue_or_cell_type
Pancreatic duct
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 289–300
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression, duct-cell and pancreatic-tissue experiments · source_derived_draft · unverified_draft
### chloride-pancreatic-exchange OSR1/SPAK activation inhibited CFTR-dependent chloride/bicarbonate exchange in the tested system. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same signaling program reduced an exchange route that could take bicarbonate back from the secretion. organism: Human and guinea pig tissue_or_cell_type: Pancreatic duct experimental_model: Expression, duct-cell and pancreatic-tissue experiments limitations: Tissue-specific response; low intracellular chloride here is a secretion signal, not dietary deficiency. exposure: Low intracellular chloride; WNK1–OSR1/SPAK activation evidence_span: {"source_cache": "artifacts/chloride-research/20398666.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc", "start_char": 0, "end_char": 1831, "text_sha256": "d013915d7024580dd55cd21d77d59aa79b2f8b0d932df8c7b8932a462d5f91cc"} [chloride-p20398666] Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. (2010). https://pubmed.ncbi.nlm.nih.gov/20398666/ DOI: 10.1053/j.gastro.2010.04.004
Complete structured claim and evidence
Cryo-EM resolved bicarbonate-bound human AE1 and identified substrate-recognition features.
Human erythrocyte anion exchanger 1 / SLC4A1 → Bicarbonate ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/37679563.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8330a7df77cf5fed0d32a5623d7e0531cacb4306d3e4356b4fcbdb591501d3ef", "start_char": 0, "end_char": 1012, "text_sha256": "8330a7df77cf5fed0d32a5623d7e0531cacb4306d3e4356b4fcbdb591501d3ef"}
experimental_model
Seven cryo-EM structures with uptake and computational analyses
exposure
Apo, bicarbonate-bound and inhibitor-bound states
limitations
Transport mechanism analysis; not a dietary chloride threshold.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human AE1
plain_language
Red cells use a dedicated anion exchanger in the system that carries carbon dioxide between tissues and lungs.
primary_references
[chloride-p37679563] Substrate binding and inhibition of the anion exchanger 1 transporter. (2023). https://pubmed.ncbi.nlm.nih.gov/37679563/ DOI: 10.1038/s41594-023-01085-6
tissue_or_cell_type
Erythrocyte anion exchanger protein
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 302–313
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven cryo-EM structures with uptake and computational analyses · source_derived_draft · unverified_draft
### chloride-ae1-bicarbonate Cryo-EM resolved bicarbonate-bound human AE1 and identified substrate-recognition features. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Red cells use a dedicated anion exchanger in the system that carries carbon dioxide between tissues and lungs. organism: Human AE1 tissue_or_cell_type: Erythrocyte anion exchanger protein experimental_model: Seven cryo-EM structures with uptake and computational analyses limitations: Transport mechanism analysis; not a dietary chloride threshold. exposure: Apo, bicarbonate-bound and inhibitor-bound states evidence_span: {"source_cache": "artifacts/chloride-research/37679563.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8330a7df77cf5fed0d32a5623d7e0531cacb4306d3e4356b4fcbdb591501d3ef", "start_char": 0, "end_char": 1012, "text_sha256": "8330a7df77cf5fed0d32a5623d7e0531cacb4306d3e4356b4fcbdb591501d3ef"} [chloride-p37679563] Substrate binding and inhibition of the anion exchanger 1 transporter. (2023). https://pubmed.ncbi.nlm.nih.gov/37679563/ DOI: 10.1038/s41594-023-01085-6
Complete structured claim and evidence
Chloride opposed osmolyte-stimulated WNK1 autophosphorylation.
Chloride ion → Human WNK lysine deficient protein kinase 1 / WNK1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/33689398.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9", "start_char": 0, "end_char": 1308, "text_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9"}
experimental_model
Biochemistry and structural measurements
exposure
PEG400 or ethylene glycol osmotic challenge
limitations
Artificial osmolytes; supports additional regulation, not a universal chloride-only switch.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human WNK1 and WNK3 constructs
plain_language
Water balance and chloride jointly influence the kinase.
primary_references
[chloride-p33689398] Osmosensing by WNK Kinases. (2021). https://pubmed.ncbi.nlm.nih.gov/33689398/ DOI: 10.1091/mbc.e20-01-0089
tissue_or_cell_type
Purified kinase domains
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 341–352
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemistry and structural measurements · source_derived_draft · unverified_draft
### chloride-wnk1-osmotic Chloride opposed osmolyte-stimulated WNK1 autophosphorylation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Water balance and chloride jointly influence the kinase. organism: Human WNK1 and WNK3 constructs tissue_or_cell_type: Purified kinase domains experimental_model: Biochemistry and structural measurements limitations: Artificial osmolytes; supports additional regulation, not a universal chloride-only switch. exposure: PEG400 or ethylene glycol osmotic challenge evidence_span: {"source_cache": "artifacts/chloride-research/33689398.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9", "start_char": 0, "end_char": 1308, "text_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9"} [chloride-p33689398] Osmosensing by WNK Kinases. (2021). https://pubmed.ncbi.nlm.nih.gov/33689398/ DOI: 10.1091/mbc.e20-01-0089
Complete structured claim and evidence
Chloride also opposed osmolyte-stimulated WNK3 autophosphorylation.
Chloride ion → Human WNK lysine deficient protein kinase 3 / WNK3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/33689398.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9", "start_char": 0, "end_char": 1308, "text_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9"}
experimental_model
Biochemistry and structural measurements
exposure
PEG400 or ethylene glycol osmotic challenge
limitations
Artificial osmolytes; supports additional regulation, not a universal chloride-only switch.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human WNK1 and WNK3 constructs
plain_language
Related kinases can share this regulation while remaining separate proteins.
primary_references
[chloride-p33689398] Osmosensing by WNK Kinases. (2021). https://pubmed.ncbi.nlm.nih.gov/33689398/ DOI: 10.1091/mbc.e20-01-0089
tissue_or_cell_type
Purified kinase domains
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 354–365
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemistry and structural measurements · source_derived_draft · unverified_draft
### chloride-wnk3-osmotic Chloride also opposed osmolyte-stimulated WNK3 autophosphorylation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Related kinases can share this regulation while remaining separate proteins. organism: Human WNK1 and WNK3 constructs tissue_or_cell_type: Purified kinase domains experimental_model: Biochemistry and structural measurements limitations: Artificial osmolytes; supports additional regulation, not a universal chloride-only switch. exposure: PEG400 or ethylene glycol osmotic challenge evidence_span: {"source_cache": "artifacts/chloride-research/33689398.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9", "start_char": 0, "end_char": 1308, "text_sha256": "8a51e7a42ab9c614abf2c38e22f5d563d5416fffa11b7aec5919ee221a94e1b9"} [chloride-p33689398] Osmosensing by WNK Kinases. (2021). https://pubmed.ncbi.nlm.nih.gov/33689398/ DOI: 10.1091/mbc.e20-01-0089
Complete structured claim and evidence
WNK1 E388 mutations reduced potassium inhibition while retaining kinase activity.
Potassium ion → Human WNK lysine deficient protein kinase 1 / WNK1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/42186973.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa", "start_char": 0, "end_char": 1266, "text_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa"}
experimental_model
Crystallography and mutagenesis
exposure
Cesium surrogate and potassium-inhibition assays
limitations
Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human WNK1/WNK3 constructs
plain_language
Potassium can regulate WNK1 directly as well as through changes in cell voltage and chloride.
primary_references
[chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825
tissue_or_cell_type
Purified kinase domains
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 367–378
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography and mutagenesis · source_derived_draft · unverified_draft
### chloride-wnk1-potassium WNK1 E388 mutations reduced potassium inhibition while retaining kinase activity. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium can regulate WNK1 directly as well as through changes in cell voltage and chloride. organism: Human WNK1/WNK3 constructs tissue_or_cell_type: Purified kinase domains experimental_model: Crystallography and mutagenesis limitations: Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing. exposure: Cesium surrogate and potassium-inhibition assays evidence_span: {"source_cache": "artifacts/chloride-research/42186973.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa", "start_char": 0, "end_char": 1266, "text_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa"} [chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825
Complete structured claim and evidence
Mutation of the corresponding WNK3 E314 site reduced potassium inhibition.
Potassium ion → Human WNK lysine deficient protein kinase 3 / WNK3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/42186973.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa", "start_char": 0, "end_char": 1266, "text_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa"}
experimental_model
Crystallography and mutagenesis
exposure
Cesium surrogate and potassium-inhibition assays
limitations
Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human WNK1/WNK3 constructs
plain_language
The direct potassium-sensitive route also has evidence in WNK3.
primary_references
[chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825
tissue_or_cell_type
Purified kinase domains
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 380–391
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography and mutagenesis · source_derived_draft · unverified_draft
### chloride-wnk3-potassium Mutation of the corresponding WNK3 E314 site reduced potassium inhibition. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The direct potassium-sensitive route also has evidence in WNK3. organism: Human WNK1/WNK3 constructs tissue_or_cell_type: Purified kinase domains experimental_model: Crystallography and mutagenesis limitations: Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing. exposure: Cesium surrogate and potassium-inhibition assays evidence_span: {"source_cache": "artifacts/chloride-research/42186973.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa", "start_char": 0, "end_char": 1266, "text_sha256": "2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa"} [chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825
Complete structured claim and evidence
Suppressing KCC2 shifted the GABA-A reversal potential in a positive direction in mature neurons.
Rat potassium/chloride cotransporter KCC2 / Slc12a5 → Reversal potential of neuronal GABA-A responses source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"}
experimental_model
Developmental expression and antisense suppression
exposure
KCC2 expression during maturation; antisense inhibition
limitations
Neuronal gradient mechanism; dietary chloride restriction is not the intervention.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Rat
plain_language
GABA’s electrical effect depends on the chloride gradient maintained by the cell.
primary_references
[chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697
tissue_or_cell_type
Hippocampal pyramidal neurons
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 406–417
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Developmental expression and antisense suppression · source_derived_draft · unverified_draft
### chloride-kcc2-gaba-loss Suppressing KCC2 shifted the GABA-A reversal potential in a positive direction in mature neurons. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: GABA’s electrical effect depends on the chloride gradient maintained by the cell. organism: Rat tissue_or_cell_type: Hippocampal pyramidal neurons experimental_model: Developmental expression and antisense suppression limitations: Neuronal gradient mechanism; dietary chloride restriction is not the intervention. exposure: KCC2 expression during maturation; antisense inhibition evidence_span: {"source_cache": "artifacts/chloride-research/9930699.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6", "start_char": 0, "end_char": 1181, "text_sha256": "2ef63b1f73a7a33ae3fc709c3ace45a585604d86f9fe1bce8c83405d21cdcaa6"} [chloride-p9930699] The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. (1999). https://pubmed.ncbi.nlm.nih.gov/9930699/ DOI: 10.1038/16697
Complete structured claim and evidence
Nkcc1 deletion attenuated GABA-triggered depolarization and calcium transients during early hippocampal development.
Mouse sodium-potassium-chloride cotransporter NKCC1 / Slc12a2 → GABA-triggered neuronal depolarization source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/19295148.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f", "start_char": 0, "end_char": 982, "text_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f"}
experimental_model
Nkcc1 knockout and neuronal activity measurements
exposure
Nkcc1 deletion
limitations
Developmental hippocampal model; does not generalize to every immature neuron.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
Chloride loading can help GABA excite developing neurons in this specific circuit.
primary_references
[chloride-p19295148] NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. (2009). https://pubmed.ncbi.nlm.nih.gov/19295148/ DOI: 10.1523/jneurosci.1377-08.2009
tissue_or_cell_type
Early postnatal hippocampal CA1 network
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 419–430
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nkcc1 knockout and neuronal activity measurements · source_derived_draft · unverified_draft
### chloride-nkcc1-gaba Nkcc1 deletion attenuated GABA-triggered depolarization and calcium transients during early hippocampal development. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride loading can help GABA excite developing neurons in this specific circuit. organism: Mouse tissue_or_cell_type: Early postnatal hippocampal CA1 network experimental_model: Nkcc1 knockout and neuronal activity measurements limitations: Developmental hippocampal model; does not generalize to every immature neuron. exposure: Nkcc1 deletion evidence_span: {"source_cache": "artifacts/chloride-research/19295148.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f", "start_char": 0, "end_char": 982, "text_sha256": "55bc6d4f9cf1d9a44f4d6c851dabd587bb2ffb7a337f67c5f9e7bfe8aefa870f"} [chloride-p19295148] NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. (2009). https://pubmed.ncbi.nlm.nih.gov/19295148/ DOI: 10.1523/jneurosci.1377-08.2009
Complete structured claim and evidence
Nkcc1-null immature retinal neurons retained approximately 30 mM intracellular chloride, similar to controls.
Mouse sodium-potassium-chloride cotransporter NKCC1 / Slc12a2 → Intracellular chloride concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/17493914.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd076a380016c2d7dfe9d765dc9e9daedf2e97387bd0730b1e2d23c8cd294a4d", "start_char": 0, "end_char": 1748, "text_sha256": "dd076a380016c2d7dfe9d765dc9e9daedf2e97387bd0730b1e2d23c8cd294a4d"}
experimental_model
Nkcc1 knockout, inhibitors and chloride imaging
exposure
Postnatal days 0–5; deletion and bumetanide
limitations
Different neuronal population from hippocampal studies; residual chloride loading mechanism unresolved.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
Some developing neurons maintained chloride without NKCC1, so the hippocampal mechanism is not universal.
primary_references
[chloride-p17493914] NKCC1 does not accumulate chloride in developing retinal neurons. (2007). https://pubmed.ncbi.nlm.nih.gov/17493914/ DOI: 10.1152/jn.00288.2007
tissue_or_cell_type
Immature retinal amacrine and ganglion cells
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 432–443
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nkcc1 knockout, inhibitors and chloride imaging · source_derived_draft · unverified_draft
### chloride-retinal-nkcc1-null Nkcc1-null immature retinal neurons retained approximately 30 mM intracellular chloride, similar to controls. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some developing neurons maintained chloride without NKCC1, so the hippocampal mechanism is not universal. organism: Mouse tissue_or_cell_type: Immature retinal amacrine and ganglion cells experimental_model: Nkcc1 knockout, inhibitors and chloride imaging limitations: Different neuronal population from hippocampal studies; residual chloride loading mechanism unresolved. exposure: Postnatal days 0–5; deletion and bumetanide evidence_span: {"source_cache": "artifacts/chloride-research/17493914.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd076a380016c2d7dfe9d765dc9e9daedf2e97387bd0730b1e2d23c8cd294a4d", "start_char": 0, "end_char": 1748, "text_sha256": "dd076a380016c2d7dfe9d765dc9e9daedf2e97387bd0730b1e2d23c8cd294a4d"} [chloride-p17493914] NKCC1 does not accumulate chloride in developing retinal neurons. (2007). https://pubmed.ncbi.nlm.nih.gov/17493914/ DOI: 10.1152/jn.00288.2007
Complete structured claim and evidence
SERT Asn101 experiments linked chloride binding to concentrative serotonin uptake.
Chloride ion → Cellular serotonin uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/21730057.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af", "start_char": 0, "end_char": 691, "text_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af"}
experimental_model
Mutagenesis, flux measurements and modeling
exposure
Asn101 substitutions and chloride-coupling assays
limitations
Transporter mechanism; no evidence that dietary chloride changes treat a mood disorder.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human SERT
plain_language
Chloride participates in neurotransmitter retrieval as well as in electrical signaling.
primary_references
[chloride-p21730057] A conserved asparagine residue in transmembrane segment 1 (TM1) of serotonin transporter dictates chloride-coupled neurotransmitter transport. (2011). https://pubmed.ncbi.nlm.nih.gov/21730057/ DOI: 10.1074/jbc.m111.250308
tissue_or_cell_type
Expressed membrane transporter
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 445–456
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutagenesis, flux measurements and modeling · source_derived_draft · unverified_draft
### chloride-sert-chloride-coupling SERT Asn101 experiments linked chloride binding to concentrative serotonin uptake. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride participates in neurotransmitter retrieval as well as in electrical signaling. organism: Human SERT tissue_or_cell_type: Expressed membrane transporter experimental_model: Mutagenesis, flux measurements and modeling limitations: Transporter mechanism; no evidence that dietary chloride changes treat a mood disorder. exposure: Asn101 substitutions and chloride-coupling assays evidence_span: {"source_cache": "artifacts/chloride-research/21730057.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af", "start_char": 0, "end_char": 691, "text_sha256": "ef83bc710cfeb47a0815a2e11c431a5bb16a8927aa81eccc38b774c0dda454af"} [chloride-p21730057] A conserved asparagine residue in transmembrane segment 1 (TM1) of serotonin transporter dictates chloride-coupled neurotransmitter transport. (2011). https://pubmed.ncbi.nlm.nih.gov/21730057/ DOI: 10.1074/jbc.m111.250308
Complete structured claim and evidence
CLCN1 linkage and a disease-associated substitution implicated the muscle chloride channel in inherited myotonia.
Human skeletal-muscle chloride channel ClC-1 / CLCN1 → Skeletal-muscle membrane hyperexcitability and myotonia source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/1379744.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbf542bf788774a420bad7ab2caa8bb57c09da9c31a285c06e9bc6ece9e1c320", "start_char": 0, "end_char": 867, "text_sha256": "bbf542bf788774a420bad7ab2caa8bb57c09da9c31a285c06e9bc6ece9e1c320"}
experimental_model
Linkage and sequence analysis
exposure
Dominant/recessive myotonia pedigrees
limitations
Early genetic report; different variants have different channel effects.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human
plain_language
Muscle stiffness can arise from faulty chloride channels despite adequate nutrient supply.
primary_references
[chloride-p1379744] The skeletal muscle chloride channel in dominant and recessive human myotonia. (1992). https://pubmed.ncbi.nlm.nih.gov/1379744/ DOI: 10.1126/science.1379744
tissue_or_cell_type
Skeletal muscle; German families
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 458–469
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Linkage and sequence analysis · source_derived_draft · unverified_draft
### chloride-clcn1-myotonia CLCN1 linkage and a disease-associated substitution implicated the muscle chloride channel in inherited myotonia. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Muscle stiffness can arise from faulty chloride channels despite adequate nutrient supply. organism: Human tissue_or_cell_type: Skeletal muscle; German families experimental_model: Linkage and sequence analysis limitations: Early genetic report; different variants have different channel effects. exposure: Dominant/recessive myotonia pedigrees evidence_span: {"source_cache": "artifacts/chloride-research/1379744.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbf542bf788774a420bad7ab2caa8bb57c09da9c31a285c06e9bc6ece9e1c320", "start_char": 0, "end_char": 867, "text_sha256": "bbf542bf788774a420bad7ab2caa8bb57c09da9c31a285c06e9bc6ece9e1c320"} [chloride-p1379744] The skeletal muscle chloride channel in dominant and recessive human myotonia. (1992). https://pubmed.ncbi.nlm.nih.gov/1379744/ DOI: 10.1126/science.1379744
Complete structured claim and evidence
Deleting LRRC8A abolished VRAC currents; reconstitution required LRRC8A with another LRRC8 isoform.
Human LRRC8A / SWELL1 → LRRC8 heteromeric volume-regulated anion channel / VRAC source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/24790029.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334", "start_char": 0, "end_char": 896, "text_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334"}
experimental_model
Genome-wide screen, gene disruption and rescue
exposure
LRRC8 knockout and isoform coexpression
limitations
Channel composition and cellular volume response; no dietary intervention.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human cell lines
plain_language
A swelling-responsive anion channel is a protein assembly, not one interchangeable subunit.
primary_references
[chloride-p24790029] Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. (2014). https://pubmed.ncbi.nlm.nih.gov/24790029/ DOI: 10.1126/science.1252826
tissue_or_cell_type
Plasma membrane
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 471–482
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genome-wide screen, gene disruption and rescue · source_derived_draft · unverified_draft
### chloride-lrrc8a-vrac Deleting LRRC8A abolished VRAC currents; reconstitution required LRRC8A with another LRRC8 isoform. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A swelling-responsive anion channel is a protein assembly, not one interchangeable subunit. organism: Human cell lines tissue_or_cell_type: Plasma membrane experimental_model: Genome-wide screen, gene disruption and rescue limitations: Channel composition and cellular volume response; no dietary intervention. exposure: LRRC8 knockout and isoform coexpression evidence_span: {"source_cache": "artifacts/chloride-research/24790029.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334", "start_char": 0, "end_char": 896, "text_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334"} [chloride-p24790029] Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. (2014). https://pubmed.ncbi.nlm.nih.gov/24790029/ DOI: 10.1126/science.1252826
Complete structured claim and evidence
Regulatory cell-volume decrease depended on LRRC8 proteins.
LRRC8 heteromeric volume-regulated anion channel / VRAC → Regulatory cell-volume decrease source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/24790029.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334", "start_char": 0, "end_char": 896, "text_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334"}
experimental_model
Genome-wide screen, gene disruption and rescue
exposure
LRRC8 knockout and isoform coexpression
limitations
Channel composition and cellular volume response; no dietary intervention.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human cell lines
plain_language
Cells use anion movement as part of their response to swelling.
primary_references
[chloride-p24790029] Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. (2014). https://pubmed.ncbi.nlm.nih.gov/24790029/ DOI: 10.1126/science.1252826
tissue_or_cell_type
Plasma membrane
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 484–495
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genome-wide screen, gene disruption and rescue · source_derived_draft · unverified_draft
### chloride-vrac-volume Regulatory cell-volume decrease depended on LRRC8 proteins. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells use anion movement as part of their response to swelling. organism: Human cell lines tissue_or_cell_type: Plasma membrane experimental_model: Genome-wide screen, gene disruption and rescue limitations: Channel composition and cellular volume response; no dietary intervention. exposure: LRRC8 knockout and isoform coexpression evidence_span: {"source_cache": "artifacts/chloride-research/24790029.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334", "start_char": 0, "end_char": 896, "text_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334"} [chloride-p24790029] Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. (2014). https://pubmed.ncbi.nlm.nih.gov/24790029/ DOI: 10.1126/science.1252826
Complete structured claim and evidence
Taurine flux depended on LRRC8 proteins in the tested cells.
LRRC8 heteromeric volume-regulated anion channel / VRAC → Cellular taurine efflux source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/24790029.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334", "start_char": 0, "end_char": 896, "text_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334"}
experimental_model
Genome-wide screen, gene disruption and rescue
exposure
LRRC8 knockout and isoform coexpression
limitations
Channel composition and cellular volume response; no dietary intervention.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human cell lines
plain_language
The channel system also connects chloride handling to movement of an organic osmolyte.
primary_references
[chloride-p24790029] Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. (2014). https://pubmed.ncbi.nlm.nih.gov/24790029/ DOI: 10.1126/science.1252826
tissue_or_cell_type
Plasma membrane
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 497–508
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genome-wide screen, gene disruption and rescue · source_derived_draft · unverified_draft
### chloride-vrac-taurine Taurine flux depended on LRRC8 proteins in the tested cells. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The channel system also connects chloride handling to movement of an organic osmolyte. organism: Human cell lines tissue_or_cell_type: Plasma membrane experimental_model: Genome-wide screen, gene disruption and rescue limitations: Channel composition and cellular volume response; no dietary intervention. exposure: LRRC8 knockout and isoform coexpression evidence_span: {"source_cache": "artifacts/chloride-research/24790029.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334", "start_char": 0, "end_char": 896, "text_sha256": "9fc0ba50276b74ac5cd7aa29c4c8af4917132a43259b45363b5c16a19b775334"} [chloride-p24790029] Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. (2014). https://pubmed.ncbi.nlm.nih.gov/24790029/ DOI: 10.1126/science.1252826
Complete structured claim and evidence
Serum bicarbonate was 27.4 versus 24 meq/L in pendrin-null and control mice.
Mouse pendrin / Slc26a4 → Plasma bicarbonate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/20375274.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953", "start_char": 0, "end_char": 1797, "text_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953"}
experimental_model
Pendrin knockout and isolated collecting-duct perfusion
exposure
Slc26a4 deletion
limitations
Residual exchange remained; baseline urine chloride excretion was unchanged.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
A local transporter defect changed the blood acid–base measurement.
primary_references
[chloride-p20375274] Deletion of the anion exchanger Slc26a4 (pendrin) decreases apical Cl(-)/HCO3(-) exchanger activity and impairs bicarbonate secretion in kidney collecting duct. (2010). https://pubmed.ncbi.nlm.nih.gov/20375274/ DOI: 10.1152/ajpcell.00033.2010
tissue_or_cell_type
Non-acid-secreting intercalated cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 523–534
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pendrin knockout and isolated collecting-duct perfusion · source_derived_draft · unverified_draft
### chloride-pendrin-blood-bicarbonate Serum bicarbonate was 27.4 versus 24 meq/L in pendrin-null and control mice. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A local transporter defect changed the blood acid–base measurement. organism: Mouse tissue_or_cell_type: Non-acid-secreting intercalated cells experimental_model: Pendrin knockout and isolated collecting-duct perfusion limitations: Residual exchange remained; baseline urine chloride excretion was unchanged. exposure: Slc26a4 deletion evidence_span: {"source_cache": "artifacts/chloride-research/20375274.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953", "start_char": 0, "end_char": 1797, "text_sha256": "8ddda637993b80b24351aefe0451312d849175bd3ec2f3af23b72b50f7439953"} [chloride-p20375274] Deletion of the anion exchanger Slc26a4 (pendrin) decreases apical Cl(-)/HCO3(-) exchanger activity and impairs bicarbonate secretion in kidney collecting duct. (2010). https://pubmed.ncbi.nlm.nih.gov/20375274/ DOI: 10.1152/ajpcell.00033.2010
Complete structured claim and evidence
Slc4a8 deletion abolished the thiazide-sensitive NaCl absorption measured in cortical collecting ducts.
Mouse sodium-driven chloride/bicarbonate exchanger / Slc4a8 → Renal sodium reabsorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/20389022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb", "start_char": 0, "end_char": 1550, "text_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb"}
experimental_model
Gene deletion and perfused collecting ducts
exposure
Slc4a8, NCC and ENaC perturbations
limitations
Mouse electroneutral transport; thiazide sensitivity alone does not identify NCC.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
Sodium and chloride can be reabsorbed through a coupled exchanger system beyond NCC.
primary_references
[chloride-p20389022] The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. (2010). https://pubmed.ncbi.nlm.nih.gov/20389022/ DOI: 10.1172/jci40145
tissue_or_cell_type
Cortical collecting duct
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 536–547
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene deletion and perfused collecting ducts · source_derived_draft · unverified_draft
### chloride-ndcbe-sodium Slc4a8 deletion abolished the thiazide-sensitive NaCl absorption measured in cortical collecting ducts. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium and chloride can be reabsorbed through a coupled exchanger system beyond NCC. organism: Mouse tissue_or_cell_type: Cortical collecting duct experimental_model: Gene deletion and perfused collecting ducts limitations: Mouse electroneutral transport; thiazide sensitivity alone does not identify NCC. exposure: Slc4a8, NCC and ENaC perturbations evidence_span: {"source_cache": "artifacts/chloride-research/20389022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb", "start_char": 0, "end_char": 1550, "text_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb"} [chloride-p20389022] The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. (2010). https://pubmed.ncbi.nlm.nih.gov/20389022/ DOI: 10.1172/jci40145
Complete structured claim and evidence
Isolated-duct results supported parallel pendrin and NDCBE action in electroneutral NaCl absorption.
Mouse pendrin / Slc26a4 → Renal chloride reabsorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/20389022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb", "start_char": 0, "end_char": 1550, "text_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb"}
experimental_model
Gene deletion and perfused collecting ducts
exposure
Slc4a8, NCC and ENaC perturbations
limitations
Mouse electroneutral transport; thiazide sensitivity alone does not identify NCC.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
Two separately modeled exchangers cooperate in the proposed route.
primary_references
[chloride-p20389022] The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. (2010). https://pubmed.ncbi.nlm.nih.gov/20389022/ DOI: 10.1172/jci40145
tissue_or_cell_type
Cortical collecting duct
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 549–560
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene deletion and perfused collecting ducts · source_derived_draft · unverified_draft
### chloride-pendrin-ndcbe Isolated-duct results supported parallel pendrin and NDCBE action in electroneutral NaCl absorption. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two separately modeled exchangers cooperate in the proposed route. organism: Mouse tissue_or_cell_type: Cortical collecting duct experimental_model: Gene deletion and perfused collecting ducts limitations: Mouse electroneutral transport; thiazide sensitivity alone does not identify NCC. exposure: Slc4a8, NCC and ENaC perturbations evidence_span: {"source_cache": "artifacts/chloride-research/20389022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb", "start_char": 0, "end_char": 1550, "text_sha256": "e38f38d6be0ba6db309bcc35de163f9dd6db62963c41864ca0b7fe6c24a31ddb"} [chloride-p20389022] The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. (2010). https://pubmed.ncbi.nlm.nih.gov/20389022/ DOI: 10.1172/jci40145
Complete structured claim and evidence
Adding luminal choline chloride or RbCl reduced renin release, whereas the tested sodium salts without chloride did not.
Chloride ion → Juxtaglomerular renin secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/2012204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac", "start_char": 0, "end_char": 1695, "text_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac"}
experimental_model
Perfused isolated juxtaglomerular apparatus
exposure
Luminal ion substitutions and 1 µM bumetanide
limitations
Tubular luminal signal; plasma chloride alone does not reproduce it.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Rabbit
plain_language
The kidney’s salt sensor responded specifically to chloride delivery in this experiment.
primary_references
[chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486
tissue_or_cell_type
Macula densa and renin-secreting apparatus
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 562–573
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused isolated juxtaglomerular apparatus · source_derived_draft · unverified_draft
### chloride-macula-chloride-renin Adding luminal choline chloride or RbCl reduced renin release, whereas the tested sodium salts without chloride did not. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney’s salt sensor responded specifically to chloride delivery in this experiment. organism: Rabbit tissue_or_cell_type: Macula densa and renin-secreting apparatus experimental_model: Perfused isolated juxtaglomerular apparatus limitations: Tubular luminal signal; plasma chloride alone does not reproduce it. exposure: Luminal ion substitutions and 1 µM bumetanide evidence_span: {"source_cache": "artifacts/chloride-research/2012204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac", "start_char": 0, "end_char": 1695, "text_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac"} [chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486
Complete structured claim and evidence
Luminal bumetanide increased renin release during high-NaCl perfusion, supporting cotransporter-dependent sensing.
Sodium-potassium-chloride cotransporter 2 → Juxtaglomerular renin secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/2012204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac", "start_char": 0, "end_char": 1695, "text_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac"}
experimental_model
Perfused isolated juxtaglomerular apparatus
exposure
Luminal ion substitutions and 1 µM bumetanide
limitations
Pharmacological evidence for macula-densa Na-K-2Cl transport; molecular NKCC2 was not genetically tested in this experiment.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Rabbit
plain_language
The chloride must engage the transport system to produce the usual signal.
primary_references
[chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486
tissue_or_cell_type
Macula densa and renin-secreting apparatus
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 575–586
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused isolated juxtaglomerular apparatus · source_derived_draft · unverified_draft
### chloride-macula-transport-renin Luminal bumetanide increased renin release during high-NaCl perfusion, supporting cotransporter-dependent sensing. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chloride must engage the transport system to produce the usual signal. organism: Rabbit tissue_or_cell_type: Macula densa and renin-secreting apparatus experimental_model: Perfused isolated juxtaglomerular apparatus limitations: Pharmacological evidence for macula-densa Na-K-2Cl transport; molecular NKCC2 was not genetically tested in this experiment. exposure: Luminal ion substitutions and 1 µM bumetanide evidence_span: {"source_cache": "artifacts/chloride-research/2012204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac", "start_char": 0, "end_char": 1695, "text_sha256": "8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac"} [chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486
Complete structured claim and evidence
Chloride binding influenced E233 positioning and the structural region that orients D300 in pancreatic amylase.
Chloride ion → Human pancreatic alpha-amylase / AMY2A source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/15722449.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82", "start_char": 0, "end_char": 1748, "text_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82"}
experimental_model
Structure and kinetics
exposure
N298S variant with and without chloride
limitations
N298S variant evidence; this is not a claim that all alpha-amylases require chloride.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human pancreatic alpha-amylase variant
plain_language
The ion helps position catalytic parts of the enzyme.
primary_references
[chloride-p15722449] Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase. (2005). https://pubmed.ncbi.nlm.nih.gov/15722449/ DOI: 10.1110/ps.041079305
tissue_or_cell_type
Purified digestive enzyme
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 601–612
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Structure and kinetics · source_derived_draft · unverified_draft
### chloride-amylase-geometry Chloride binding influenced E233 positioning and the structural region that orients D300 in pancreatic amylase. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The ion helps position catalytic parts of the enzyme. organism: Human pancreatic alpha-amylase variant tissue_or_cell_type: Purified digestive enzyme experimental_model: Structure and kinetics limitations: N298S variant evidence; this is not a claim that all alpha-amylases require chloride. exposure: N298S variant with and without chloride evidence_span: {"source_cache": "artifacts/chloride-research/15722449.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82", "start_char": 0, "end_char": 1748, "text_sha256": "c71785a489a9e9a0f3865c12c2b66cbf1db4c9e036f08398da846fbb766fbf82"} [chloride-p15722449] Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase. (2005). https://pubmed.ncbi.nlm.nih.gov/15722449/ DOI: 10.1110/ps.041079305
Complete structured claim and evidence
Myeloperoxidase favored thiocyanate kinetically and generated hypothiocyanite despite 100 mM chloride.
Thiocyanate ion → Chloride ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/9359420.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0", "start_char": 0, "end_char": 1700, "text_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0"}
experimental_model
Purified-enzyme substrate kinetics
exposure
100 mM chloride with varying thiocyanate
limitations
Product chemistry under assay conditions; not a recommendation to raise chloride or thiocyanate intake.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human neutrophil enzyme
plain_language
An abundant chloride pool does not mean it is the enzyme’s only substrate.
primary_references
[chloride-p9359420] Thiocyanate and chloride as competing substrates for myeloperoxidase. (1997). https://pubmed.ncbi.nlm.nih.gov/9359420/ DOI: 10.1042/bj3270487
tissue_or_cell_type
Myeloperoxidase reaction mixture
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 627–638
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme substrate kinetics · source_derived_draft · unverified_draft
### chloride-mpo-thiocyanate Myeloperoxidase favored thiocyanate kinetically and generated hypothiocyanite despite 100 mM chloride. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: An abundant chloride pool does not mean it is the enzyme’s only substrate. organism: Human neutrophil enzyme tissue_or_cell_type: Myeloperoxidase reaction mixture experimental_model: Purified-enzyme substrate kinetics limitations: Product chemistry under assay conditions; not a recommendation to raise chloride or thiocyanate intake. exposure: 100 mM chloride with varying thiocyanate evidence_span: {"source_cache": "artifacts/chloride-research/9359420.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0", "start_char": 0, "end_char": 1700, "text_sha256": "83dc6a264dfb45201104568ac58c76509aaa0fabca1f32efd25861146b4b38c0"} [chloride-p9359420] Thiocyanate and chloride as competing substrates for myeloperoxidase. (1997). https://pubmed.ncbi.nlm.nih.gov/9359420/ DOI: 10.1042/bj3270487
Complete structured claim and evidence
ClC-5 transported protons against their electrochemical gradient in coupling with anion transport.
Mammalian ClC-5 chloride/proton exchanger → Coupled chloride/proton exchange source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/16034421.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0", "start_char": 0, "end_char": 1359, "text_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0"}
experimental_model
Voltage and proton-flux measurements
exposure
Positive voltage and pore-glutamate mutation
limitations
Heterologous measurements; intracellular physiological direction depends on gradients.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mammalian ClC constructs in expression systems
plain_language
Some proteins historically called chloride channels are coupled chloride/proton exchangers.
primary_references
[chloride-p16034421] Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. (2005). https://pubmed.ncbi.nlm.nih.gov/16034421/ DOI: 10.1038/nature03720
tissue_or_cell_type
Plasma-membrane-expressed transport proteins
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 640–651
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Voltage and proton-flux measurements · source_derived_draft · unverified_draft
### chloride-clc5-exchange ClC-5 transported protons against their electrochemical gradient in coupling with anion transport. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some proteins historically called chloride channels are coupled chloride/proton exchangers. organism: Mammalian ClC constructs in expression systems tissue_or_cell_type: Plasma-membrane-expressed transport proteins experimental_model: Voltage and proton-flux measurements limitations: Heterologous measurements; intracellular physiological direction depends on gradients. exposure: Positive voltage and pore-glutamate mutation evidence_span: {"source_cache": "artifacts/chloride-research/16034421.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0", "start_char": 0, "end_char": 1359, "text_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0"} [chloride-p16034421] Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. (2005). https://pubmed.ncbi.nlm.nih.gov/16034421/ DOI: 10.1038/nature03720
Complete structured claim and evidence
ClC-4 also supported secondary active proton transport in the expression assay.
Mammalian ClC-4 chloride/proton exchanger → Coupled chloride/proton exchange source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/16034421.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0", "start_char": 0, "end_char": 1359, "text_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0"}
experimental_model
Voltage and proton-flux measurements
exposure
Positive voltage and pore-glutamate mutation
limitations
Heterologous measurements; intracellular physiological direction depends on gradients.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mammalian ClC constructs in expression systems
plain_language
The related ClC-4 protein is separately represented as an exchanger.
primary_references
[chloride-p16034421] Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. (2005). https://pubmed.ncbi.nlm.nih.gov/16034421/ DOI: 10.1038/nature03720
tissue_or_cell_type
Plasma-membrane-expressed transport proteins
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 653–664
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Voltage and proton-flux measurements · source_derived_draft · unverified_draft
### chloride-clc4-exchange ClC-4 also supported secondary active proton transport in the expression assay. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The related ClC-4 protein is separately represented as an exchanger. organism: Mammalian ClC constructs in expression systems tissue_or_cell_type: Plasma-membrane-expressed transport proteins experimental_model: Voltage and proton-flux measurements limitations: Heterologous measurements; intracellular physiological direction depends on gradients. exposure: Positive voltage and pore-glutamate mutation evidence_span: {"source_cache": "artifacts/chloride-research/16034421.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0", "start_char": 0, "end_char": 1359, "text_sha256": "3a437e5233f3bb917ef5bbfee37e6eaed1745baf86fd4f35c85d8ad509dfa0f0"} [chloride-p16034421] Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. (2005). https://pubmed.ncbi.nlm.nih.gov/16034421/ DOI: 10.1038/nature03720
Complete structured claim and evidence
Measured ClC-5 transport stoichiometry was two chloride ions per proton.
Mammalian ClC-5 chloride/proton exchanger → Chloride ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/19131966.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04e75eb135b2ed1c3a14a69b20f602132fc4a55cc0e1d3f6a11ee2834692a79e", "start_char": 0, "end_char": 1161, "text_sha256": "04e75eb135b2ed1c3a14a69b20f602132fc4a55cc0e1d3f6a11ee2834692a79e"}
experimental_model
Absolute proton-flux imaging
exposure
Proton gradients and S168 substitutions
limitations
Assay stoichiometry, not dietary requirements.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mammalian ClC-5 in Xenopus oocytes
plain_language
This protein couples chloride transport to proton movement at a measured ratio.
primary_references
[chloride-p19131966] Conversion of the 2 Cl(-)/1 H+ antiporter ClC-5 in a NO3(-)/H+ antiporter by a single point mutation. (2009). https://pubmed.ncbi.nlm.nih.gov/19131966/ DOI: 10.1038/emboj.2008.284
tissue_or_cell_type
Expressed plasma membrane
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 666–677
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Absolute proton-flux imaging · source_derived_draft · unverified_draft
### chloride-clc5-stoichiometry Measured ClC-5 transport stoichiometry was two chloride ions per proton. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: This protein couples chloride transport to proton movement at a measured ratio. organism: Mammalian ClC-5 in Xenopus oocytes tissue_or_cell_type: Expressed plasma membrane experimental_model: Absolute proton-flux imaging limitations: Assay stoichiometry, not dietary requirements. exposure: Proton gradients and S168 substitutions evidence_span: {"source_cache": "artifacts/chloride-research/19131966.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04e75eb135b2ed1c3a14a69b20f602132fc4a55cc0e1d3f6a11ee2834692a79e", "start_char": 0, "end_char": 1161, "text_sha256": "04e75eb135b2ed1c3a14a69b20f602132fc4a55cc0e1d3f6a11ee2834692a79e"} [chloride-p19131966] Conversion of the 2 Cl(-)/1 H+ antiporter ClC-5 in a NO3(-)/H+ antiporter by a single point mutation. (2009). https://pubmed.ncbi.nlm.nih.gov/19131966/ DOI: 10.1038/emboj.2008.284
Complete structured claim and evidence
Clcn5 deletion reduced both receptor-mediated and fluid-phase proximal-tubule endocytosis.
Mouse ClC-5 chloride/proton exchanger / Clcn5 → Proximal-tubule apical endocytosis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"}
experimental_model
Clcn5 knockout and uptake measurements
exposure
Clcn5 disruption
limitations
The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
A chloride-handling defect can impair kidney retrieval of filtered material.
primary_references
[chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597
tissue_or_cell_type
Proximal renal tubule
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 679–690
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn5 knockout and uptake measurements · source_derived_draft · unverified_draft
### chloride-clc5-endocytosis Clcn5 deletion reduced both receptor-mediated and fluid-phase proximal-tubule endocytosis. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A chloride-handling defect can impair kidney retrieval of filtered material. organism: Mouse tissue_or_cell_type: Proximal renal tubule experimental_model: Clcn5 knockout and uptake measurements limitations: The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated. exposure: Clcn5 disruption evidence_span: {"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"} [chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597
Complete structured claim and evidence
Tubular endocytosis of PTH was reduced in the Clcn5-null model.
Mouse ClC-5 chloride/proton exchanger / Clcn5 → Proximal-tubule uptake of luminal PTH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"}
experimental_model
Clcn5 knockout and uptake measurements
exposure
Clcn5 disruption
limitations
The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
Hormone retrieval changed too, offering a possible route to altered mineral regulation.
primary_references
[chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597
tissue_or_cell_type
Proximal renal tubule
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 705–716
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn5 knockout and uptake measurements · source_derived_draft · unverified_draft
### chloride-clc5-pth Tubular endocytosis of PTH was reduced in the Clcn5-null model. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hormone retrieval changed too, offering a possible route to altered mineral regulation. organism: Mouse tissue_or_cell_type: Proximal renal tubule experimental_model: Clcn5 knockout and uptake measurements limitations: The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated. exposure: Clcn5 disruption evidence_span: {"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"} [chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597
Complete structured claim and evidence
NaPi-2 redistributed toward intracellular vesicles at steady state despite slower internalization.
Mouse ClC-5 chloride/proton exchanger / Clcn5 → Mouse sodium-phosphate cotransporter NaPi-IIa / Slc34a1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"}
experimental_model
Clcn5 knockout and uptake measurements
exposure
Clcn5 disruption
limitations
The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
An endosomal defect changed where the phosphate transporter was located.
primary_references
[chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597
tissue_or_cell_type
Proximal renal tubule
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 718–729
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn5 knockout and uptake measurements · source_derived_draft · unverified_draft
### chloride-clc5-napi NaPi-2 redistributed toward intracellular vesicles at steady state despite slower internalization. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: An endosomal defect changed where the phosphate transporter was located. organism: Mouse tissue_or_cell_type: Proximal renal tubule experimental_model: Clcn5 knockout and uptake measurements limitations: The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated. exposure: Clcn5 disruption evidence_span: {"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"} [chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597
Complete structured claim and evidence
NHE3 also redistributed toward intracellular vesicles at steady state despite slower internalization.
Mouse ClC-5 chloride/proton exchanger / Clcn5 → Mouse sodium/hydrogen exchanger NHE3 / Slc9a3 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"}
experimental_model
Clcn5 knockout and uptake measurements
exposure
Clcn5 disruption
limitations
The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
The sodium/hydrogen exchanger changed location too.
primary_references
[chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597
tissue_or_cell_type
Proximal renal tubule
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 731–742
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn5 knockout and uptake measurements · source_derived_draft · unverified_draft
### chloride-clc5-nhe3 NHE3 also redistributed toward intracellular vesicles at steady state despite slower internalization. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sodium/hydrogen exchanger changed location too. organism: Mouse tissue_or_cell_type: Proximal renal tubule experimental_model: Clcn5 knockout and uptake measurements limitations: The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated. exposure: Clcn5 disruption evidence_span: {"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"} [chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597
Complete structured claim and evidence
Tail-current reversal potentials supported two chloride ions exchanged per proton by ClC-7/Ostm1.
Engineered plasma-membrane ClC-7/Ostm1 assay complexes → Chloride ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/21527911.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5", "start_char": 0, "end_char": 1081, "text_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5"}
experimental_model
Electrophysiology of plasma-membrane-targeted constructs
exposure
ClC-7 sorting-motif mutations and Ostm1 constructs
limitations
Engineering enabled measurement outside lysosomes. Species checked in author manuscript https://edoc.mdc-berlin.de/id/eprint/11621/1/11621oa.pdf, Results; native direction depends on gradients.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human and rat ClC-7; Xenopus oocytes and mammalian cells
plain_language
The bone-related chloride transporter is a coupled exchanger, not a simple chloride pore.
primary_references
[chloride-p21527911] ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21527911/ DOI: 10.1038/emboj.2011.137
tissue_or_cell_type
Engineered plasma membrane
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 744–755
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrophysiology of plasma-membrane-targeted constructs · source_derived_draft · unverified_draft
### chloride-clc7-stoichiometry Tail-current reversal potentials supported two chloride ions exchanged per proton by ClC-7/Ostm1. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The bone-related chloride transporter is a coupled exchanger, not a simple chloride pore. organism: Human and rat ClC-7; Xenopus oocytes and mammalian cells tissue_or_cell_type: Engineered plasma membrane experimental_model: Electrophysiology of plasma-membrane-targeted constructs limitations: Engineering enabled measurement outside lysosomes. Species checked in author manuscript https://edoc.mdc-berlin.de/id/eprint/11621/1/11621oa.pdf, Results; native direction depends on gradients. exposure: ClC-7 sorting-motif mutations and Ostm1 constructs evidence_span: {"source_cache": "artifacts/chloride-research/21527911.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5", "start_char": 0, "end_char": 1081, "text_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5"} [chloride-p21527911] ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21527911/ DOI: 10.1038/emboj.2011.137
Complete structured claim and evidence
Both the amino-terminal and transmembrane regions of Ostm1 were required for the measured ClC-7 exchange activity.
Mammalian OSTM1 ClC-7 accessory subunit → Engineered plasma-membrane ClC-7/Ostm1 assay complexes source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/21527911.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5", "start_char": 0, "end_char": 1081, "text_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5"}
experimental_model
Electrophysiology of plasma-membrane-targeted constructs
exposure
ClC-7 sorting-motif mutations and Ostm1 constructs
limitations
Engineering enabled measurement outside lysosomes. Species checked in author manuscript https://edoc.mdc-berlin.de/id/eprint/11621/1/11621oa.pdf, Results; native direction depends on gradients.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human and rat ClC-7; Xenopus oocytes and mammalian cells
plain_language
A separate accessory protein is needed for the exchanger to work.
primary_references
[chloride-p21527911] ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21527911/ DOI: 10.1038/emboj.2011.137
tissue_or_cell_type
Engineered plasma membrane
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 757–768
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrophysiology of plasma-membrane-targeted constructs · source_derived_draft · unverified_draft
### chloride-ostm1-clc7 Both the amino-terminal and transmembrane regions of Ostm1 were required for the measured ClC-7 exchange activity. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate accessory protein is needed for the exchanger to work. organism: Human and rat ClC-7; Xenopus oocytes and mammalian cells tissue_or_cell_type: Engineered plasma membrane experimental_model: Electrophysiology of plasma-membrane-targeted constructs limitations: Engineering enabled measurement outside lysosomes. Species checked in author manuscript https://edoc.mdc-berlin.de/id/eprint/11621/1/11621oa.pdf, Results; native direction depends on gradients. exposure: ClC-7 sorting-motif mutations and Ostm1 constructs evidence_span: {"source_cache": "artifacts/chloride-research/21527911.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5", "start_char": 0, "end_char": 1081, "text_sha256": "1a83cfa67615e467858b2a56c2e6b6e1ae8414a28c553b8a645d7789987f53c5"} [chloride-p21527911] ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21527911/ DOI: 10.1038/emboj.2011.137
Complete structured claim and evidence
Clcn7-null mice had severe osteopetrosis despite normal osteoclast numbers.
Mouse ClC-7 chloride/proton exchanger / Clcn7 → Osteoclastic bone resorption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/11207362.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a", "start_char": 0, "end_char": 821, "text_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a"}
experimental_model
Clcn7 knockout and human mutation identification
exposure
ClC-7 loss
limitations
Historical title calls ClC-7 a channel; current exchanger classification does not change the reported knockout phenotype. Not a dietary chloride study.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse; human infantile osteopetrosis patient
plain_language
Having bone-resorbing cells is insufficient when their transport machinery fails.
primary_references
[chloride-p11207362] Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. (2001). https://pubmed.ncbi.nlm.nih.gov/11207362/ DOI: 10.1016/s0092-8674(01)00206-9
tissue_or_cell_type
Osteoclast ruffled border
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 783–794
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn7 knockout and human mutation identification · source_derived_draft · unverified_draft
### chloride-clc7-bone Clcn7-null mice had severe osteopetrosis despite normal osteoclast numbers. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having bone-resorbing cells is insufficient when their transport machinery fails. organism: Mouse; human infantile osteopetrosis patient tissue_or_cell_type: Osteoclast ruffled border experimental_model: Clcn7 knockout and human mutation identification limitations: Historical title calls ClC-7 a channel; current exchanger classification does not change the reported knockout phenotype. Not a dietary chloride study. exposure: ClC-7 loss evidence_span: {"source_cache": "artifacts/chloride-research/11207362.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a", "start_char": 0, "end_char": 821, "text_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a"} [chloride-p11207362] Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. (2001). https://pubmed.ncbi.nlm.nih.gov/11207362/ DOI: 10.1016/s0092-8674(01)00206-9
Complete structured claim and evidence
Hyperreninemia and hyperaldosteronism accompanied the deficient-formula case and normalized after adequate feeding.
Chloride → Renin–aldosterone system activation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/7293908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4d85273187d5fba7fc6f5c38bda3da041dc4751715a0e65c995ba6898650a84", "start_char": 0, "end_char": 458, "text_sha256": "a4d85273187d5fba7fc6f5c38bda3da041dc4751715a0e65c995ba6898650a84"}
experimental_model
Infant case and formula correction
exposure
Chloride-deficient formula replaced with adequate formula
limitations
Uncontrolled historical case; formula replacement is not a universal dose-response experiment.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human
plain_language
The body’s salt-conserving hormone system responded to the shortage.
primary_references
[chloride-p7293908] Metabolic effects of chloride-deficient formula. (1981). https://pubmed.ncbi.nlm.nih.gov/7293908/
tissue_or_cell_type
Diet, growth and blood chemistry
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 809–820
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Infant case and formula correction · source_derived_draft · unverified_draft
### chloride-formula-hormones Hyperreninemia and hyperaldosteronism accompanied the deficient-formula case and normalized after adequate feeding. Condition category: nutrient_deficiency nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The body’s salt-conserving hormone system responded to the shortage. organism: Human tissue_or_cell_type: Diet, growth and blood chemistry experimental_model: Infant case and formula correction limitations: Uncontrolled historical case; formula replacement is not a universal dose-response experiment. exposure: Chloride-deficient formula replaced with adequate formula evidence_span: {"source_cache": "artifacts/chloride-research/7293908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4d85273187d5fba7fc6f5c38bda3da041dc4751715a0e65c995ba6898650a84", "start_char": 0, "end_char": 458, "text_sha256": "a4d85273187d5fba7fc6f5c38bda3da041dc4751715a0e65c995ba6898650a84"} [chloride-p7293908] Metabolic effects of chloride-deficient formula. (1981). https://pubmed.ncbi.nlm.nih.gov/7293908/
Complete structured claim and evidence
Both infants resumed normal weight gain after switching to a formula with adequate chloride.
Chloride → Infant weight gain source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/7354566.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b7b6f5d5a9768b20ea47cf913f35928464109148730676363c19c4ba39fb2c4", "start_char": 0, "end_char": 418, "text_sha256": "3b7b6f5d5a9768b20ea47cf913f35928464109148730676363c19c4ba39fb2c4"}
experimental_model
Two infant cases after a formula manufacturing error
exposure
Severely chloride-deficient soy formula replaced
limitations
Case reports; not a population prevalence estimate.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human
plain_language
Correcting the feeding problem restored growth in these cases.
primary_references
[chloride-p7354566] Failure to thrive and metabolic alkalosis. Adverse effects of a chloride-deficient formula in two infants. (1980). https://pubmed.ncbi.nlm.nih.gov/7354566/ DOI: 10.1001/jama.1980.03300360040024
tissue_or_cell_type
Nutrition and growth
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 822–833
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two infant cases after a formula manufacturing error · source_derived_draft · unverified_draft
### chloride-formula-growth Both infants resumed normal weight gain after switching to a formula with adequate chloride. Condition category: nutrient_deficiency nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting the feeding problem restored growth in these cases. organism: Human tissue_or_cell_type: Nutrition and growth experimental_model: Two infant cases after a formula manufacturing error limitations: Case reports; not a population prevalence estimate. exposure: Severely chloride-deficient soy formula replaced evidence_span: {"source_cache": "artifacts/chloride-research/7354566.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b7b6f5d5a9768b20ea47cf913f35928464109148730676363c19c4ba39fb2c4", "start_char": 0, "end_char": 418, "text_sha256": "3b7b6f5d5a9768b20ea47cf913f35928464109148730676363c19c4ba39fb2c4"} [chloride-p7354566] Failure to thrive and metabolic alkalosis. Adverse effects of a chloride-deficient formula in two infants. (1980). https://pubmed.ncbi.nlm.nih.gov/7354566/ DOI: 10.1001/jama.1980.03300360040024
Complete structured claim and evidence
Urinary bicarbonate excretion increased during correction of chloride-depletion alkalosis.
Potassium chloride → Urinary bicarbonate excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/2450456.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7", "start_char": 0, "end_char": 1348, "text_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7"}
experimental_model
Human depletion–repletion balance experiment
exposure
Furosemide plus restricted NaCl; oral KCl repletion over 36 hours
limitations
Loss-associated depletion; KCl supplies potassium too. Mechanism does not imply self-treatment or apply to every alkalosis.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human men
plain_language
The kidney began removing more of the excess bicarbonate.
primary_references
[chloride-p2450456] On the mechanism by which chloride corrects metabolic alkalosis in man. (1988). https://pubmed.ncbi.nlm.nih.gov/2450456/ DOI: 10.1016/0002-9343(88)90265-3
tissue_or_cell_type
Kidney and systemic acid–base balance
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 848–859
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human depletion–repletion balance experiment · source_derived_draft · unverified_draft
### chloride-repletion-bicarbonaturia Urinary bicarbonate excretion increased during correction of chloride-depletion alkalosis. Condition category: nutrient_deficiency nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney began removing more of the excess bicarbonate. organism: Human men tissue_or_cell_type: Kidney and systemic acid–base balance experimental_model: Human depletion–repletion balance experiment limitations: Loss-associated depletion; KCl supplies potassium too. Mechanism does not imply self-treatment or apply to every alkalosis. exposure: Furosemide plus restricted NaCl; oral KCl repletion over 36 hours evidence_span: {"source_cache": "artifacts/chloride-research/2450456.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7", "start_char": 0, "end_char": 1348, "text_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7"} [chloride-p2450456] On the mechanism by which chloride corrects metabolic alkalosis in man. (1988). https://pubmed.ncbi.nlm.nih.gov/2450456/ DOI: 10.1016/0002-9343(88)90265-3
Complete structured claim and evidence
The same KCl load did not change acid–base status in sodium-depleted subjects who were not chloride-depleted.
Potassium chloride → Plasma bicarbonate concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/2450456.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7", "start_char": 0, "end_char": 1348, "text_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7"}
experimental_model
Human depletion–repletion balance experiment
exposure
Furosemide plus restricted NaCl; oral KCl repletion over 36 hours
limitations
Loss-associated depletion; KCl supplies potassium too. Mechanism does not imply self-treatment or apply to every alkalosis.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human men
plain_language
The response depended on chloride depletion, not merely on receiving KCl.
primary_references
[chloride-p2450456] On the mechanism by which chloride corrects metabolic alkalosis in man. (1988). https://pubmed.ncbi.nlm.nih.gov/2450456/ DOI: 10.1016/0002-9343(88)90265-3
tissue_or_cell_type
Kidney and systemic acid–base balance
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 861–872
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human depletion–repletion balance experiment · source_derived_draft · unverified_draft
### chloride-repletion-control The same KCl load did not change acid–base status in sodium-depleted subjects who were not chloride-depleted. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response depended on chloride depletion, not merely on receiving KCl. organism: Human men tissue_or_cell_type: Kidney and systemic acid–base balance experimental_model: Human depletion–repletion balance experiment limitations: Loss-associated depletion; KCl supplies potassium too. Mechanism does not imply self-treatment or apply to every alkalosis. exposure: Furosemide plus restricted NaCl; oral KCl repletion over 36 hours evidence_span: {"source_cache": "artifacts/chloride-research/2450456.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7", "start_char": 0, "end_char": 1348, "text_sha256": "3df006f26c20c11aeb8fd26884ccbd5d1389921d34a40adad6f72edc184360d7"} [chloride-p2450456] On the mechanism by which chloride corrects metabolic alkalosis in man. (1988). https://pubmed.ncbi.nlm.nih.gov/2450456/ DOI: 10.1016/0002-9343(88)90265-3
Complete structured claim and evidence
CF sweat ducts showed low chloride permeability and impaired NaCl reabsorption.
Chloride ion → Sweat-duct sodium chloride reabsorption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/6823316.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce2ab2d15d30590a4e4d13e12060fc8656238cea8856a2aad03ed9e2e4dcee4", "start_char": 0, "end_char": 642, "text_sha256": "8ce2ab2d15d30590a4e4d13e12060fc8656238cea8856a2aad03ed9e2e4dcee4"}
experimental_model
Microperfusion of isolated sweat ducts
exposure
Cystic fibrosis versus control
limitations
Predates molecular CFTR identification; does not equate sweat chloride with blood chloride.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human controls and cystic fibrosis patients
plain_language
A salty sweat measurement can reflect failure to reclaim salt, not excessive intake.
primary_references
[chloride-p6823316] Chloride impermeability in cystic fibrosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6823316/ DOI: 10.1038/301421a0
tissue_or_cell_type
Sweat duct
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 874–885
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microperfusion of isolated sweat ducts · source_derived_draft · unverified_draft
### chloride-sweat-reabsorption CF sweat ducts showed low chloride permeability and impaired NaCl reabsorption. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A salty sweat measurement can reflect failure to reclaim salt, not excessive intake. organism: Human controls and cystic fibrosis patients tissue_or_cell_type: Sweat duct experimental_model: Microperfusion of isolated sweat ducts limitations: Predates molecular CFTR identification; does not equate sweat chloride with blood chloride. exposure: Cystic fibrosis versus control evidence_span: {"source_cache": "artifacts/chloride-research/6823316.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8ce2ab2d15d30590a4e4d13e12060fc8656238cea8856a2aad03ed9e2e4dcee4", "start_char": 0, "end_char": 642, "text_sha256": "8ce2ab2d15d30590a4e4d13e12060fc8656238cea8856a2aad03ed9e2e4dcee4"} [chloride-p6823316] Chloride impermeability in cystic fibrosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6823316/ DOI: 10.1038/301421a0
Complete structured claim and evidence
CLCNKB loss-of-function variants caused renal salt-wasting hypokalemic alkalosis in the studied families.
Chloride channel ClC-Kb → Renal chloride reabsorption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/9326936.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e", "start_char": 0, "end_char": 1227, "text_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e"}
experimental_model
Genetics in seventeen kindreds
exposure
Loss-of-function CLCNKB variants
limitations
This cohort had normal magnesium and variable calciuria; do not universalize the full phenotype.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human
plain_language
A chloride-channel defect can drive loss of other electrolytes.
primary_references
[chloride-p9326936] Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. (1997). https://pubmed.ncbi.nlm.nih.gov/9326936/ DOI: 10.1038/ng1097-171
tissue_or_cell_type
Renal salt handling
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 887–898
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetics in seventeen kindreds · source_derived_draft · unverified_draft
### chloride-clcnkb-salt CLCNKB loss-of-function variants caused renal salt-wasting hypokalemic alkalosis in the studied families. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A chloride-channel defect can drive loss of other electrolytes. organism: Human tissue_or_cell_type: Renal salt handling experimental_model: Genetics in seventeen kindreds limitations: This cohort had normal magnesium and variable calciuria; do not universalize the full phenotype. exposure: Loss-of-function CLCNKB variants evidence_span: {"source_cache": "artifacts/chloride-research/9326936.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e", "start_char": 0, "end_char": 1227, "text_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e"} [chloride-p9326936] Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. (1997). https://pubmed.ncbi.nlm.nih.gov/9326936/ DOI: 10.1038/ng1097-171
Complete structured claim and evidence
Affected CLCNKB families had hypokalemia alongside salt wasting.
Chloride channel ClC-Kb → Plasma potassium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/9326936.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e", "start_char": 0, "end_char": 1227, "text_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e"}
experimental_model
Genetics in seventeen kindreds
exposure
Loss-of-function CLCNKB variants
limitations
This cohort had normal magnesium and variable calciuria; do not universalize the full phenotype.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human
plain_language
Potassium deficiency can be downstream of defective chloride transport.
primary_references
[chloride-p9326936] Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. (1997). https://pubmed.ncbi.nlm.nih.gov/9326936/ DOI: 10.1038/ng1097-171
tissue_or_cell_type
Renal salt handling
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 900–911
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetics in seventeen kindreds · source_derived_draft · unverified_draft
### chloride-clcnkb-potassium Affected CLCNKB families had hypokalemia alongside salt wasting. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium deficiency can be downstream of defective chloride transport. organism: Human tissue_or_cell_type: Renal salt handling experimental_model: Genetics in seventeen kindreds limitations: This cohort had normal magnesium and variable calciuria; do not universalize the full phenotype. exposure: Loss-of-function CLCNKB variants evidence_span: {"source_cache": "artifacts/chloride-research/9326936.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e", "start_char": 0, "end_char": 1227, "text_sha256": "80ade45b4ae654e5aa13b671daebab418640aa033aca3a74cae4ccf52d4e279e"} [chloride-p9326936] Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. (1997). https://pubmed.ncbi.nlm.nih.gov/9326936/ DOI: 10.1038/ng1097-171
Complete structured claim and evidence
Knockout patch-clamp studies identified ClC-K2 as a major basolateral chloride channel in the tested nephron segments.
Mouse ClC-K2 basolateral chloride channel / Clcnk2 → Renal chloride reabsorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/27335120.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3", "start_char": 0, "end_char": 1432, "text_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3"}
experimental_model
Clcnk2 knockout and nephron patch clamp
exposure
Gene deletion; furosemide/thiazide responses
limitations
Mouse ortholog; not a claim of dietary chloride deficiency.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
Chloride needs a route out of the back of kidney cells as well as a route in.
primary_references
[chloride-p27335120] The ClC-K2 Chloride Channel Is Critical for Salt Handling in the Distal Nephron. (2017). https://pubmed.ncbi.nlm.nih.gov/27335120/ DOI: 10.1681/asn.2016010085
tissue_or_cell_type
Thick ascending limb and distal nephron
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 913–924
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcnk2 knockout and nephron patch clamp · source_derived_draft · unverified_draft
### chloride-clcnk2-basolateral Knockout patch-clamp studies identified ClC-K2 as a major basolateral chloride channel in the tested nephron segments. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride needs a route out of the back of kidney cells as well as a route in. organism: Mouse tissue_or_cell_type: Thick ascending limb and distal nephron experimental_model: Clcnk2 knockout and nephron patch clamp limitations: Mouse ortholog; not a claim of dietary chloride deficiency. exposure: Gene deletion; furosemide/thiazide responses evidence_span: {"source_cache": "artifacts/chloride-research/27335120.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3", "start_char": 0, "end_char": 1432, "text_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3"} [chloride-p27335120] The ClC-K2 Chloride Channel Is Critical for Salt Handling in the Distal Nephron. (2017). https://pubmed.ncbi.nlm.nih.gov/27335120/ DOI: 10.1681/asn.2016010085
Complete structured claim and evidence
ClC-K2-null mice lacked the usual furosemide natriuretic response and had a severely blunted thiazide response.
Mouse ClC-K2 basolateral chloride channel / Clcnk2 → Renal response to loop diuretics source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/27335120.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3", "start_char": 0, "end_char": 1432, "text_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3"}
experimental_model
Clcnk2 knockout and nephron patch clamp
exposure
Gene deletion; furosemide/thiazide responses
limitations
Mouse ortholog; not a claim of dietary chloride deficiency.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Mouse
plain_language
A transporter defect changed how two diuretic classes worked.
primary_references
[chloride-p27335120] The ClC-K2 Chloride Channel Is Critical for Salt Handling in the Distal Nephron. (2017). https://pubmed.ncbi.nlm.nih.gov/27335120/ DOI: 10.1681/asn.2016010085
tissue_or_cell_type
Thick ascending limb and distal nephron
trigger_kind
machinery_impairment Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 926–937
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcnk2 knockout and nephron patch clamp · source_derived_draft · unverified_draft
### chloride-clcnk2-diuretics ClC-K2-null mice lacked the usual furosemide natriuretic response and had a severely blunted thiazide response. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter defect changed how two diuretic classes worked. organism: Mouse tissue_or_cell_type: Thick ascending limb and distal nephron experimental_model: Clcnk2 knockout and nephron patch clamp limitations: Mouse ortholog; not a claim of dietary chloride deficiency. exposure: Gene deletion; furosemide/thiazide responses evidence_span: {"source_cache": "artifacts/chloride-research/27335120.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3", "start_char": 0, "end_char": 1432, "text_sha256": "0a0a14e0cc6fd76c451f92665dfed0255edcaf0355b46414f91c74d977f5d6b3"} [chloride-p27335120] The ClC-K2 Chloride Channel Is Critical for Salt Handling in the Distal Nephron. (2017). https://pubmed.ncbi.nlm.nih.gov/27335120/ DOI: 10.1681/asn.2016010085
Complete structured claim and evidence
Hypochloremia was associated with poor diuretic response in the heart-failure cohort.
Plasma or serum chloride concentration → Renal response to loop diuretics source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/chloride-research/27507113.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927", "start_char": 0, "end_char": 2050, "text_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927"}
experimental_model
Observational cohort and separate uncontrolled pilot
exposure
162-person cohort; ten-person pilot, lysine chloride 115 mmol/day for three days
limitations
Association does not establish causality; the small pilot did not prove clinical benefit or survival improvement.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human heart failure patients
plain_language
A low blood measurement identified a pattern, without proving what caused it.
primary_references
[chloride-p27507113] Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights. (2016). https://pubmed.ncbi.nlm.nih.gov/27507113/ DOI: 10.1161/circheartfailure.116.003180
tissue_or_cell_type
Blood and renal diuretic response
trigger_kind
biomarker_context Imported condition classification; unverified.
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 939–950
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Observational cohort and separate uncontrolled pilot · source_derived_draft · unverified_draft
### chloride-heart-marker Hypochloremia was associated with poor diuretic response in the heart-failure cohort. Condition category: biomarker_context nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low blood measurement identified a pattern, without proving what caused it. organism: Human heart failure patients tissue_or_cell_type: Blood and renal diuretic response experimental_model: Observational cohort and separate uncontrolled pilot limitations: Association does not establish causality; the small pilot did not prove clinical benefit or survival improvement. exposure: 162-person cohort; ten-person pilot, lysine chloride 115 mmol/day for three days evidence_span: {"source_cache": "artifacts/chloride-research/27507113.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927", "start_char": 0, "end_char": 2050, "text_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927"} [chloride-p27507113] Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights. (2016). https://pubmed.ncbi.nlm.nih.gov/27507113/ DOI: 10.1161/circheartfailure.116.003180
Complete structured claim and evidence
The pilot reported a mean serum chloride rise of 2.2 mmol/L after sodium-free lysine chloride supplementation.
Lysine chloride experimental supplement → Plasma or serum chloride concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/27507113.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927", "start_char": 0, "end_char": 2050, "text_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927"}
experimental_model
Observational cohort and separate uncontrolled pilot
exposure
162-person cohort; ten-person pilot, lysine chloride 115 mmol/day for three days
limitations
Association does not establish causality; the small pilot did not prove clinical benefit or survival improvement.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human heart failure patients
plain_language
The study tested a way to supply chloride without sodium; benefit remains unresolved.
primary_references
[chloride-p27507113] Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights. (2016). https://pubmed.ncbi.nlm.nih.gov/27507113/ DOI: 10.1161/circheartfailure.116.003180
tissue_or_cell_type
Blood and renal diuretic response
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 952–963
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Observational cohort and separate uncontrolled pilot · source_derived_draft · unverified_draft
### chloride-lysine-chloride The pilot reported a mean serum chloride rise of 2.2 mmol/L after sodium-free lysine chloride supplementation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study tested a way to supply chloride without sodium; benefit remains unresolved. organism: Human heart failure patients tissue_or_cell_type: Blood and renal diuretic response experimental_model: Observational cohort and separate uncontrolled pilot limitations: Association does not establish causality; the small pilot did not prove clinical benefit or survival improvement. exposure: 162-person cohort; ten-person pilot, lysine chloride 115 mmol/day for three days evidence_span: {"source_cache": "artifacts/chloride-research/27507113.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927", "start_char": 0, "end_char": 2050, "text_sha256": "978879bf8054ce7c99ef939133966e618cc8030cb7bd624e250ce32002455927"} [chloride-p27507113] Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights. (2016). https://pubmed.ncbi.nlm.nih.gov/27507113/ DOI: 10.1161/circheartfailure.116.003180
Complete structured claim and evidence
The fall in strong-ion difference was greater after saline than Plasma-Lyte.
0.9% sodium chloride intravenous solution → Plasma strong-ion difference source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/22580944.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814", "start_char": 0, "end_char": 1757, "text_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814"}
experimental_model
Randomized blinded crossover
exposure
2 L saline or Plasma-Lyte 148 over one hour
limitations
IV fluid formulations differ in several components; short-term perfusion is not kidney failure or dietary salt exposure.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Twelve healthy adult men
plain_language
The balance of strong ions changed alongside the chloride rise.
primary_references
[chloride-p22580944] A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. (2012). https://pubmed.ncbi.nlm.nih.gov/22580944/ DOI: 10.1097/sla.0b013e318256be72
tissue_or_cell_type
Renal MRI and blood chemistry
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 978–989
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized blinded crossover · source_derived_draft · unverified_draft
### chloride-saline-sid The fall in strong-ion difference was greater after saline than Plasma-Lyte. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The balance of strong ions changed alongside the chloride rise. organism: Twelve healthy adult men tissue_or_cell_type: Renal MRI and blood chemistry experimental_model: Randomized blinded crossover limitations: IV fluid formulations differ in several components; short-term perfusion is not kidney failure or dietary salt exposure. exposure: 2 L saline or Plasma-Lyte 148 over one hour evidence_span: {"source_cache": "artifacts/chloride-research/22580944.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814", "start_char": 0, "end_char": 1757, "text_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814"} [chloride-p22580944] A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. (2012). https://pubmed.ncbi.nlm.nih.gov/22580944/ DOI: 10.1097/sla.0b013e318256be72
Complete structured claim and evidence
Renal cortical perfusion fell from baseline after saline but not Plasma-Lyte.
0.9% sodium chloride intravenous solution → Renal cortical tissue perfusion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/22580944.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814", "start_char": 0, "end_char": 1757, "text_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814"}
experimental_model
Randomized blinded crossover
exposure
2 L saline or Plasma-Lyte 148 over one hour
limitations
IV fluid formulations differ in several components; short-term perfusion is not kidney failure or dietary salt exposure.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Twelve healthy adult men
plain_language
A short-term kidney blood-flow measure changed; this alone does not prove tissue injury.
primary_references
[chloride-p22580944] A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. (2012). https://pubmed.ncbi.nlm.nih.gov/22580944/ DOI: 10.1097/sla.0b013e318256be72
tissue_or_cell_type
Renal MRI and blood chemistry
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 991–1002
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized blinded crossover · source_derived_draft · unverified_draft
### chloride-saline-perfusion Renal cortical perfusion fell from baseline after saline but not Plasma-Lyte. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A short-term kidney blood-flow measure changed; this alone does not prove tissue injury. organism: Twelve healthy adult men tissue_or_cell_type: Renal MRI and blood chemistry experimental_model: Randomized blinded crossover limitations: IV fluid formulations differ in several components; short-term perfusion is not kidney failure or dietary salt exposure. exposure: 2 L saline or Plasma-Lyte 148 over one hour evidence_span: {"source_cache": "artifacts/chloride-research/22580944.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814", "start_char": 0, "end_char": 1757, "text_sha256": "7d2fb56addfe8ab376d6b086ad5d0da5220a0f6ceaa5733612d927ad2edb1814"} [chloride-p22580944] A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. (2012). https://pubmed.ncbi.nlm.nih.gov/22580944/ DOI: 10.1097/sla.0b013e318256be72
Complete structured claim and evidence
MAKE30 occurred in 14.3% with balanced crystalloids versus 15.4% with saline (P=0.04).
Balanced crystalloid intravenous solutions (formulation specified per claim) → Major adverse kidney event within 30 days / MAKE30 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/29485925.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10dfa6509546c1ed6e3ef5ebf45e595574e58e70aca47dbb2bd372c71ffa333a", "start_char": 0, "end_char": 1901, "text_sha256": "10dfa6509546c1ed6e3ef5ebf45e595574e58e70aca47dbb2bd372c71ffa333a"}
experimental_model
SMART pragmatic cluster-randomized crossover
exposure
Balanced crystalloids versus saline
limitations
Composite primary endpoint; mortality and separate renal components were not individually significant. Not chloride-only randomization.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
15,802 critically ill adults
plain_language
One large trial favored balanced fluid for a combined kidney-and-death endpoint.
primary_references
[chloride-p29485925] Balanced Crystalloids versus Saline in Critically Ill Adults. (2018). https://pubmed.ncbi.nlm.nih.gov/29485925/ DOI: 10.1056/nejmoa1711584
tissue_or_cell_type
Five ICUs at one academic center
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 1004–1015
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SMART pragmatic cluster-randomized crossover · source_derived_draft · unverified_draft
### chloride-smart-composite MAKE30 occurred in 14.3% with balanced crystalloids versus 15.4% with saline (P=0.04). Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: One large trial favored balanced fluid for a combined kidney-and-death endpoint. organism: 15,802 critically ill adults tissue_or_cell_type: Five ICUs at one academic center experimental_model: SMART pragmatic cluster-randomized crossover limitations: Composite primary endpoint; mortality and separate renal components were not individually significant. Not chloride-only randomization. exposure: Balanced crystalloids versus saline evidence_span: {"source_cache": "artifacts/chloride-research/29485925.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10dfa6509546c1ed6e3ef5ebf45e595574e58e70aca47dbb2bd372c71ffa333a", "start_char": 0, "end_char": 1901, "text_sha256": "10dfa6509546c1ed6e3ef5ebf45e595574e58e70aca47dbb2bd372c71ffa333a"} [chloride-p29485925] Balanced Crystalloids versus Saline in Critically Ill Adults. (2018). https://pubmed.ncbi.nlm.nih.gov/29485925/ DOI: 10.1056/nejmoa1711584
Complete structured claim and evidence
Ninety-day mortality was 21.8% versus 22.0% with balanced fluid and saline (P=0.90).
Balanced crystalloid intravenous solutions (formulation specified per claim) → Death within 90 days source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/35041780.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "93fd07a116ddc28d056e36eb8aa72edd0666af1d402fe9a297fc5698d9d62e70", "start_char": 0, "end_char": 2031, "text_sha256": "93fd07a116ddc28d056e36eb8aa72edd0666af1d402fe9a297fc5698d9d62e70"}
experimental_model
PLUS double-blind randomized trial
exposure
Plasma-Lyte 148 versus saline
limitations
Different primary outcome and design from SMART; a nonsignificant difference does not prove equivalence or isolate chloride.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
5,037 critically ill adults
plain_language
A later trial did not show a survival benefit.
primary_references
[chloride-p35041780] Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. (2022). https://pubmed.ncbi.nlm.nih.gov/35041780/ DOI: 10.1056/nejmoa2114464
tissue_or_cell_type
53 Australian/New Zealand ICUs
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 1017–1028
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PLUS double-blind randomized trial · source_derived_draft · unverified_draft
### chloride-plus-mortality Ninety-day mortality was 21.8% versus 22.0% with balanced fluid and saline (P=0.90). Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A later trial did not show a survival benefit. organism: 5,037 critically ill adults tissue_or_cell_type: 53 Australian/New Zealand ICUs experimental_model: PLUS double-blind randomized trial limitations: Different primary outcome and design from SMART; a nonsignificant difference does not prove equivalence or isolate chloride. exposure: Plasma-Lyte 148 versus saline evidence_span: {"source_cache": "artifacts/chloride-research/35041780.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "93fd07a116ddc28d056e36eb8aa72edd0666af1d402fe9a297fc5698d9d62e70", "start_char": 0, "end_char": 2031, "text_sha256": "93fd07a116ddc28d056e36eb8aa72edd0666af1d402fe9a297fc5698d9d62e70"} [chloride-p35041780] Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. (2022). https://pubmed.ncbi.nlm.nih.gov/35041780/ DOI: 10.1056/nejmoa2114464
Complete structured claim and evidence
New renal-replacement therapy occurred in 12.7% versus 12.9%; the difference confidence interval included zero.
Balanced crystalloid intravenous solutions (formulation specified per claim) → New renal-replacement therapy source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/35041780.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "93fd07a116ddc28d056e36eb8aa72edd0666af1d402fe9a297fc5698d9d62e70", "start_char": 0, "end_char": 2031, "text_sha256": "93fd07a116ddc28d056e36eb8aa72edd0666af1d402fe9a297fc5698d9d62e70"}
experimental_model
PLUS double-blind randomized trial
exposure
Plasma-Lyte 148 versus saline
limitations
Different primary outcome and design from SMART; a nonsignificant difference does not prove equivalence or isolate chloride.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
5,037 critically ill adults
plain_language
The later trial also did not show a clear dialysis benefit.
primary_references
[chloride-p35041780] Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. (2022). https://pubmed.ncbi.nlm.nih.gov/35041780/ DOI: 10.1056/nejmoa2114464
tissue_or_cell_type
53 Australian/New Zealand ICUs
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 1030–1041
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PLUS double-blind randomized trial · source_derived_draft · unverified_draft
### chloride-plus-rrt New renal-replacement therapy occurred in 12.7% versus 12.9%; the difference confidence interval included zero. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: The later trial also did not show a clear dialysis benefit. organism: 5,037 critically ill adults tissue_or_cell_type: 53 Australian/New Zealand ICUs experimental_model: PLUS double-blind randomized trial limitations: Different primary outcome and design from SMART; a nonsignificant difference does not prove equivalence or isolate chloride. exposure: Plasma-Lyte 148 versus saline evidence_span: {"source_cache": "artifacts/chloride-research/35041780.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "93fd07a116ddc28d056e36eb8aa72edd0666af1d402fe9a297fc5698d9d62e70", "start_char": 0, "end_char": 2031, "text_sha256": "93fd07a116ddc28d056e36eb8aa72edd0666af1d402fe9a297fc5698d9d62e70"} [chloride-p35041780] Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. (2022). https://pubmed.ncbi.nlm.nih.gov/35041780/ DOI: 10.1056/nejmoa2114464
Complete structured claim and evidence
Pendrin knockdown did not change measured Calu-3 bicarbonate secretion.
Human pendrin / SLC26A4 → Airway epithelial bicarbonate secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/29536650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9da6a23e90b30ab4d0c2b537af65076e93cc3370470f64a9dafdeaaff525f157", "start_char": 0, "end_char": 1519, "text_sha256": "9da6a23e90b30ab4d0c2b537af65076e93cc3370470f64a9dafdeaaff525f157"}
experimental_model
Knockdown and epithelial secretion assays
exposure
Pendrin shRNA, CFTR deficiency, culture conditions
limitations
Authors explicitly limit extrapolation to other airway epithelia.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human Calu-3 cell line
plain_language
One airway model relied mainly on CFTR, despite detectable pendrin.
primary_references
[chloride-p29536650] Most bicarbonate secretion by Calu-3 cells is mediated by CFTR and independent of pendrin. (2018). https://pubmed.ncbi.nlm.nih.gov/29536650/ DOI: 10.14814/phy2.13641
tissue_or_cell_type
Airway gland-like epithelial model
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 1043–1054
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Knockdown and epithelial secretion assays · source_derived_draft · unverified_draft
### chloride-calu3-pendrin-null Pendrin knockdown did not change measured Calu-3 bicarbonate secretion. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: One airway model relied mainly on CFTR, despite detectable pendrin. organism: Human Calu-3 cell line tissue_or_cell_type: Airway gland-like epithelial model experimental_model: Knockdown and epithelial secretion assays limitations: Authors explicitly limit extrapolation to other airway epithelia. exposure: Pendrin shRNA, CFTR deficiency, culture conditions evidence_span: {"source_cache": "artifacts/chloride-research/29536650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9da6a23e90b30ab4d0c2b537af65076e93cc3370470f64a9dafdeaaff525f157", "start_char": 0, "end_char": 1519, "text_sha256": "9da6a23e90b30ab4d0c2b537af65076e93cc3370470f64a9dafdeaaff525f157"} [chloride-p29536650] Most bicarbonate secretion by Calu-3 cells is mediated by CFTR and independent of pendrin. (2018). https://pubmed.ncbi.nlm.nih.gov/29536650/ DOI: 10.14814/phy2.13641
Complete structured claim and evidence
IL-4-induced pendrin supported chloride/bicarbonate exchange in primary airway surface cultures.
Human pendrin / SLC26A4 → Airway epithelial bicarbonate secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/30742493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a", "start_char": 0, "end_char": 1882, "text_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a"}
experimental_model
Primary epithelial cultures and native tissue
exposure
IL-4 induction and pendrin knockdown
limitations
Inflamed surface epithelium differs from Calu-3; no universal airway assignment.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human nasal and bronchial epithelia
plain_language
Different airway cells can use a different balance of the same transport proteins.
primary_references
[chloride-p30742493] Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia. (2019). https://pubmed.ncbi.nlm.nih.gov/30742493/ DOI: 10.1165/rcmb.2018-0158oc
tissue_or_cell_type
Ciliated airway surface
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 1056–1067
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary epithelial cultures and native tissue · source_derived_draft · unverified_draft
### chloride-surface-pendrin IL-4-induced pendrin supported chloride/bicarbonate exchange in primary airway surface cultures. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different airway cells can use a different balance of the same transport proteins. organism: Human nasal and bronchial epithelia tissue_or_cell_type: Ciliated airway surface experimental_model: Primary epithelial cultures and native tissue limitations: Inflamed surface epithelium differs from Calu-3; no universal airway assignment. exposure: IL-4 induction and pendrin knockdown evidence_span: {"source_cache": "artifacts/chloride-research/30742493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a", "start_char": 0, "end_char": 1882, "text_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a"} [chloride-p30742493] Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia. (2019). https://pubmed.ncbi.nlm.nih.gov/30742493/ DOI: 10.1165/rcmb.2018-0158oc
Complete structured claim and evidence
Inducing pendrin approximately doubled the forskolin-stimulated CFTR-sensitive current in the tested cells.
Human pendrin / SLC26A4 → CFTR anion conductance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/30742493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a", "start_char": 0, "end_char": 1882, "text_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a"}
experimental_model
Primary epithelial cultures and native tissue
exposure
IL-4 induction and pendrin knockdown
limitations
Inflamed surface epithelium differs from Calu-3; no universal airway assignment.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human nasal and bronchial epithelia
plain_language
One transporter can influence another channel’s measured activity.
primary_references
[chloride-p30742493] Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia. (2019). https://pubmed.ncbi.nlm.nih.gov/30742493/ DOI: 10.1165/rcmb.2018-0158oc
tissue_or_cell_type
Ciliated airway surface
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 1069–1080
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary epithelial cultures and native tissue · source_derived_draft · unverified_draft
### chloride-surface-pendrin-cftr Inducing pendrin approximately doubled the forskolin-stimulated CFTR-sensitive current in the tested cells. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: One transporter can influence another channel’s measured activity. organism: Human nasal and bronchial epithelia tissue_or_cell_type: Ciliated airway surface experimental_model: Primary epithelial cultures and native tissue limitations: Inflamed surface epithelium differs from Calu-3; no universal airway assignment. exposure: IL-4 induction and pendrin knockdown evidence_span: {"source_cache": "artifacts/chloride-research/30742493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a", "start_char": 0, "end_char": 1882, "text_sha256": "1ff038684ceacd46ad1e237d0cf13337924ec0f611d00a373cd3cbeeeb31864a"} [chloride-p30742493] Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia. (2019). https://pubmed.ncbi.nlm.nih.gov/30742493/ DOI: 10.1165/rcmb.2018-0158oc
Complete structured claim and evidence
Low-K medium lowered intracellular chloride in HEK293 and mDCT cells; depolarizing Kir4.1 mutants increased it.
Potassium ion → Intracellular chloride concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Extracellular K controls the intracellular chloride signal.
evidence_location
Figure 6A-B; Figure S5.
experimental_model
Cell culture and Kir4.1 mutant comparisons
limitations
HEK chloride and WNK expression differ from native DCT.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Homo sapiens; Mus musculus cell lines
plain_language
A change outside the cell can change chloride inside, connecting potassium sensing to salt transport.
primary_references
[terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006
tissue_or_cell_type
HEK293 and mDCT cells
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 125–136
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell culture and Kir4.1 mutant comparisons · source_derived_draft · unverified_draft
### renal-low-external-k-lowers-cell-chloride Low-K medium lowered intracellular chloride in HEK293 and mDCT cells; depolarizing Kir4.1 mutants increased it. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A change outside the cell can change chloride inside, connecting potassium sensing to salt transport. organism: Homo sapiens; Mus musculus cell lines tissue_or_cell_type: HEK293 and mDCT cells experimental_model: Cell culture and Kir4.1 mutant comparisons limitations: HEK chloride and WNK expression differ from native DCT. cross_nutrient: Extracellular K controls the intracellular chloride signal. evidence_location: Figure 6A-B; Figure S5. [terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006
Complete structured claim and evidence
Increasing chloride inhibited recombinant WNK4 phosphorylation of SPAK more strongly than WNK1/3 in matched assays.
Chloride ion → WNK lysine deficient protein kinase 4 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Chloride concentration gates a kinase linking K sensing to Na transport.
evidence_location
Figure 3; equimolar chloride/gluconate kinase assay.
experimental_model
Purified kinase domains; SPAK substrate
limitations
Does not directly measure native DCT chloride or WNK4 autophosphorylation.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Recombinant proteins
plain_language
Chloride restrains WNK4, a kinase upstream of sodium-chloride transport.
primary_references
[terker-2016-wnk4-chloride] Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4814375/ DOI: 10.1038/ki.2015.289
tissue_or_cell_type
Cell-free assay
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 138–149
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified kinase domains; SPAK substrate · source_derived_draft · unverified_draft
### renal-chloride-inhibits-wnk4 Increasing chloride inhibited recombinant WNK4 phosphorylation of SPAK more strongly than WNK1/3 in matched assays. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chloride restrains WNK4, a kinase upstream of sodium-chloride transport. organism: Recombinant proteins tissue_or_cell_type: Cell-free assay experimental_model: Purified kinase domains; SPAK substrate limitations: Does not directly measure native DCT chloride or WNK4 autophosphorylation. cross_nutrient: Chloride concentration gates a kinase linking K sensing to Na transport. evidence_location: Figure 3; equimolar chloride/gluconate kinase assay. [terker-2016-wnk4-chloride] Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4814375/ DOI: 10.1038/ki.2015.289
Complete structured claim and evidence
Catalytically active WNK4 phosphorylated and activated SPAK in biochemical assays.
WNK lysine deficient protein kinase 4 → STE20/SPS1-related proline/alanine-rich kinase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
This kinase relay can regulate sodium/chloride transport downstream of K sensing.
evidence_location
Primary abstract; kinase-activity and substrate-phosphorylation experiments.
experimental_model
Recombinant kinase assay
limitations
Establishes biochemical capability; not dietary potassium regulation by itself.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Recombinant proteins
plain_language
WNK4 passes a phosphate signal to SPAK.
primary_references
[vitari-2005-wnk-spak-osr1] The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases (2005). https://pubmed.ncbi.nlm.nih.gov/16083423/ DOI: 10.1042/BJ20051180
tissue_or_cell_type
Cell-free assay
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 151–162
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant kinase assay · source_derived_draft · unverified_draft
### renal-wnk4-activates-spak Catalytically active WNK4 phosphorylated and activated SPAK in biochemical assays. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: WNK4 passes a phosphate signal to SPAK. organism: Recombinant proteins tissue_or_cell_type: Cell-free assay experimental_model: Recombinant kinase assay limitations: Establishes biochemical capability; not dietary potassium regulation by itself. cross_nutrient: This kinase relay can regulate sodium/chloride transport downstream of K sensing. evidence_location: Primary abstract; kinase-activity and substrate-phosphorylation experiments. [vitari-2005-wnk-spak-osr1] The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases (2005). https://pubmed.ncbi.nlm.nih.gov/16083423/ DOI: 10.1042/BJ20051180
Complete structured claim and evidence
SPAK phosphorylated human NCC at Thr46, Thr55 and Thr60; Thr60 mutation impaired chloride-depletion-induced NCC activation.
STE20/SPS1-related proline/alanine-rich kinase → Thiazide-sensitive sodium-chloride cotransporter source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Defines the sodium/chloride transporter step of the potassium switch.
evidence_location
Primary abstract; phosphosite mapping, docking and Thr60Ala assays.
experimental_model
Recombinant phosphosite mapping and cell mutants
limitations
The dietary K response was not tested in this experiment.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Human protein; HEK293/mpkDCT cells
plain_language
A kinase modifies the sodium-chloride transporter at regulatory sites.
primary_references
[richardson-2008-spak-osr1-ncc] Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1 (2008). https://pubmed.ncbi.nlm.nih.gov/18270262/ DOI: 10.1242/jcs.025312
tissue_or_cell_type
Biochemical assay and cultured kidney-derived cells
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 164–175
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant phosphosite mapping and cell mutants · source_derived_draft · unverified_draft
### renal-stk39-phosphorylates-ncc SPAK phosphorylated human NCC at Thr46, Thr55 and Thr60; Thr60 mutation impaired chloride-depletion-induced NCC activation. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase modifies the sodium-chloride transporter at regulatory sites. organism: Human protein; HEK293/mpkDCT cells tissue_or_cell_type: Biochemical assay and cultured kidney-derived cells experimental_model: Recombinant phosphosite mapping and cell mutants limitations: The dietary K response was not tested in this experiment. cross_nutrient: Defines the sodium/chloride transporter step of the potassium switch. evidence_location: Primary abstract; phosphosite mapping, docking and Thr60Ala assays. [richardson-2008-spak-osr1-ncc] Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1 (2008). https://pubmed.ncbi.nlm.nih.gov/18270262/ DOI: 10.1242/jcs.025312
Complete structured claim and evidence
OSR1 phosphorylated human NCC at Thr46, Thr55 and Thr60; Thr60 mutation impaired chloride-depletion-induced NCC activation.
Oxidative stress responsive kinase 1 → Thiazide-sensitive sodium-chloride cotransporter source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Defines the sodium/chloride transporter step of the potassium switch.
evidence_location
Primary abstract; phosphosite mapping, docking and Thr60Ala assays.
experimental_model
Recombinant phosphosite mapping and cell mutants
limitations
The dietary K response was not tested in this experiment.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Human protein; HEK293/mpkDCT cells
plain_language
A kinase modifies the sodium-chloride transporter at regulatory sites.
primary_references
[richardson-2008-spak-osr1-ncc] Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1 (2008). https://pubmed.ncbi.nlm.nih.gov/18270262/ DOI: 10.1242/jcs.025312
tissue_or_cell_type
Biochemical assay and cultured kidney-derived cells
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 177–188
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant phosphosite mapping and cell mutants · source_derived_draft · unverified_draft
### renal-oxsr1-phosphorylates-ncc OSR1 phosphorylated human NCC at Thr46, Thr55 and Thr60; Thr60 mutation impaired chloride-depletion-induced NCC activation. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase modifies the sodium-chloride transporter at regulatory sites. organism: Human protein; HEK293/mpkDCT cells tissue_or_cell_type: Biochemical assay and cultured kidney-derived cells experimental_model: Recombinant phosphosite mapping and cell mutants limitations: The dietary K response was not tested in this experiment. cross_nutrient: Defines the sodium/chloride transporter step of the potassium switch. evidence_location: Primary abstract; phosphosite mapping, docking and Thr60Ala assays. [richardson-2008-spak-osr1-ncc] Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1 (2008). https://pubmed.ncbi.nlm.nih.gov/18270262/ DOI: 10.1242/jcs.025312
Complete structured claim and evidence
Low-potassium feeding on high salt reduced sodium excretion; NCC deletion blunted the blood-pressure response.
Thiazide-sensitive sodium-chloride cotransporter → Renal sodium reabsorption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Potassium restriction changes sodium handling through NCC.
evidence_location
Figure 2A-C.
experimental_model
Wild-type versus Slc12a3-null dietary study
limitations
Knockout tests pathway contribution, not exclusive control of pressure.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Mus musculus
plain_language
Potassium scarcity can make sodium retention easier through NCC.
primary_references
[terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006
tissue_or_cell_type
Kidney
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 112–123
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type versus Slc12a3-null dietary study · source_derived_draft · unverified_draft
### renal-low-k-ncc-salt-retention Low-potassium feeding on high salt reduced sodium excretion; NCC deletion blunted the blood-pressure response. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium scarcity can make sodium retention easier through NCC. organism: Mus musculus tissue_or_cell_type: Kidney experimental_model: Wild-type versus Slc12a3-null dietary study limitations: Knockout tests pathway contribution, not exclusive control of pressure. cross_nutrient: Potassium restriction changes sodium handling through NCC. evidence_location: Figure 2A-C. [terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006
Complete structured claim and evidence
Cloned renal NKCC2 supported bumetanide-sensitive sodium-potassium-chloride cotransport in oocytes, distinct from NCC potassium-independent NaCl transport.
Sodium-potassium-chloride cotransporter 2 → NKCC2-mediated ion influx source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Potassium is a transported participant in this sodium/chloride entry mechanism.
evidence_location
Primary abstract; functional oocyte characterization.
experimental_model
Cloned renal cotransporter expression
limitations
Transport identity, not a dietary deficiency threshold; individual splice variants are not generalized.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Mammalian proteins in Xenopus laevis oocytes
plain_language
NKCC2 moves potassium together with sodium and chloride; the related NCC transporter does not require potassium as cargo.
primary_references
[gamba-1994-nkcc2] Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney (1994). https://www.sciencedirect.com/science/article/pii/S0021925817324997 DOI: 10.1016/S0021-9258(17)32499-7
tissue_or_cell_type
Heterologous cell membrane
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 548–559
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloned renal cotransporter expression · source_derived_draft · unverified_draft
### renal-nkcc2-couples-potassium-to-salt-influx Cloned renal NKCC2 supported bumetanide-sensitive sodium-potassium-chloride cotransport in oocytes, distinct from NCC potassium-independent NaCl transport. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: NKCC2 moves potassium together with sodium and chloride; the related NCC transporter does not require potassium as cargo. organism: Mammalian proteins in Xenopus laevis oocytes tissue_or_cell_type: Heterologous cell membrane experimental_model: Cloned renal cotransporter expression limitations: Transport identity, not a dietary deficiency threshold; individual splice variants are not generalized. cross_nutrient: Potassium is a transported participant in this sodium/chloride entry mechanism. evidence_location: Primary abstract; functional oocyte characterization. [gamba-1994-nkcc2] Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney (1994). https://www.sciencedirect.com/science/article/pii/S0021925817324997 DOI: 10.1016/S0021-9258(17)32499-7
Complete structured claim and evidence
Expression of human pendrin increased chloride transport in Xenopus oocytes and Sf9 cells, alongside increased iodide transport.
Human pendrin / SLC26A4 → Chloride ion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Human pendrin expressed in Xenopus oocytes and Sf9 insect cells
exposure
PDS cRNA microinjection or recombinant baculovirus expression; concentrations not provided in abstract.
limitations
This demonstrates shared anion transport capability, not that dietary chloride deficiency blocks iodine repletion.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Human protein in Xenopus laevis and Spodoptera frugiperda cells
plain_language
Pendrin handles chloride as well as iodide.
primary_references
[iodine-trans-pendrin-halides1999] The Pendred syndrome gene encodes a chloride-iodide transport protein. (1999). https://pubmed.ncbi.nlm.nih.gov/10192399/ DOI: 10.1038/7783
tissue_or_cell_type
Heterologous cell membranes
transport_effect
depends Pendrin is an anion exchanger and the record reports increased transport without naming its direction.
transport_pool
the cytosol across the plasma membrane Pendrin is an anion exchanger and the record reports increased transport without naming its direction.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 310–321
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human pendrin expressed in Xenopus oocytes and Sf9 insect cells · source_derived_draft · unverified_draft
### iodine-trans-pendrin-chloride Expression of human pendrin increased chloride transport in Xenopus oocytes and Sf9 cells, alongside increased iodide transport. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pendrin handles chloride as well as iodide. organism: Human protein in Xenopus laevis and Spodoptera frugiperda cells tissue_or_cell_type: Heterologous cell membranes experimental_model: Human pendrin expressed in Xenopus oocytes and Sf9 insect cells limitations: This demonstrates shared anion transport capability, not that dietary chloride deficiency blocks iodine repletion. exposure: PDS cRNA microinjection or recombinant baculovirus expression; concentrations not provided in abstract. cross_nutrient: true [iodine-trans-pendrin-halides1999] The Pendred syndrome gene encodes a chloride-iodide transport protein. (1999). https://pubmed.ncbi.nlm.nih.gov/10192399/ DOI: 10.1038/7783
Complete structured claim and evidence
Human SLC26A7 expression in HEK293T cells generated chloride and iodide currents that increased when bath halide concentrations rose from 50 to 149 mM.
Human SLC26A7 anion transporter → Iodide ion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp
exposure
Whole-cell patch clamp 24 hours after 2 micrograms plasmid transfection; 50/149 mM total halide conditions; voltage steps from −100 to +100 mV.
limitations
Halide concentrations greatly exceed physiological iodide; transport capacity does not settle net thyroid iodide flux, stoichiometry or localization.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens
plain_language
Human SLC26A7 can carry both chloride and iodide under controlled laboratory conditions.
primary_references
[iodine-trans-slc26a7-structure2025] Structural basis for substrate recognition mechanism of human SLC26A7. (2025). https://pubmed.ncbi.nlm.nih.gov/40817112/ DOI: 10.1038/s41467-025-62792-w
tissue_or_cell_type
HEK293T plasma membrane
transport_effect
depends Recorded as a halide current that rose with bath halide concentration, so the direction follows the gradient.
transport_pool
the cytosol across the plasma membrane Recorded as a halide current that rose with bath halide concentration, so the direction follows the gradient.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 466–477
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp · source_derived_draft · unverified_draft
### iodine-trans-a7-halide-current2025 Human SLC26A7 expression in HEK293T cells generated chloride and iodide currents that increased when bath halide concentrations rose from 50 to 149 mM. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human SLC26A7 can carry both chloride and iodide under controlled laboratory conditions. organism: Homo sapiens tissue_or_cell_type: HEK293T plasma membrane experimental_model: Purified human SLC26A7 cryo-EM; recombinant human SLC26A7 in HEK293T cells with whole-cell patch clamp limitations: Halide concentrations greatly exceed physiological iodide; transport capacity does not settle net thyroid iodide flux, stoichiometry or localization. exposure: Whole-cell patch clamp 24 hours after 2 micrograms plasmid transfection; 50/149 mM total halide conditions; voltage steps from −100 to +100 mV. cross_nutrient: true [iodine-trans-slc26a7-structure2025] Structural basis for substrate recognition mechanism of human SLC26A7. (2025). https://pubmed.ncbi.nlm.nih.gov/40817112/ DOI: 10.1038/s41467-025-62792-w
Complete structured claim and evidence
Fasting achlorhydric participants absorbed substantially less calcium from carbonate than from citrate.
Calcium carbonate → Intestinal calcium absorption source_derived_draftungraded
Experimental context and source evidence
experimental_model
11 achlorhydric patients and nine controls; 250 mg calcium isotope tests.
exposure
Fasting achlorhydric mean fractions: carbonate 0.042, citrate 0.452; normal subjects showed no significant formulation difference.
limitations
Not evidence that carbonate always fails or citrate always outperforms it.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
Low stomach acid can change how a calcium preparation is absorbed.
primary_references
[cal-clin-recker1985] Calcium absorption and achlorhydria (1985). https://pubmed.ncbi.nlm.nih.gov/4000241/ DOI: 10.1056/NEJM198507113130202
tissue_or_cell_type
Human clinical or absorption endpoint
Calcium: mechanism-first literature curation (2026-09-17) · lines 1164–1174
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 11 achlorhydric patients and nine controls; 250 mg calcium isotope tests. · source_derived_draft · unverified_draft
### cal-carbonate-fasting-achlorhydria Fasting achlorhydric participants absorbed substantially less calcium from carbonate than from citrate. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low stomach acid can change how a calcium preparation is absorbed. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: 11 achlorhydric patients and nine controls; 250 mg calcium isotope tests. limitations: Not evidence that carbonate always fails or citrate always outperforms it. exposure: Fasting achlorhydric mean fractions: carbonate 0.042, citrate 0.452; normal subjects showed no significant formulation difference. [cal-clin-recker1985] Calcium absorption and achlorhydria (1985). https://pubmed.ncbi.nlm.nih.gov/4000241/ DOI: 10.1056/NEJM198507113130202
Complete structured claim and evidence
Calcium carbonate given with a normal breakfast showed normal absorption in the achlorhydric participants.
Calcium carbonate → Intestinal calcium absorption source_derived_draftungraded
Experimental context and source evidence
experimental_model
Meal comparison in the achlorhydria absorption study.
limitations
Small study; the meal experiment did not isolate a molecular rescue mechanism.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
The meal changed the result seen during fasting.
primary_references
[cal-clin-recker1985] Calcium absorption and achlorhydria (1985). https://pubmed.ncbi.nlm.nih.gov/4000241/ DOI: 10.1056/NEJM198507113130202
tissue_or_cell_type
Human clinical or absorption endpoint
Calcium: mechanism-first literature curation (2026-09-17) · lines 1176–1185
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Meal comparison in the achlorhydria absorption study. · source_derived_draft · unverified_draft
### cal-carbonate-meal-achlorhydria Calcium carbonate given with a normal breakfast showed normal absorption in the achlorhydric participants. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The meal changed the result seen during fasting. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: Meal comparison in the achlorhydria absorption study. limitations: Small study; the meal experiment did not isolate a molecular rescue mechanism. [cal-clin-recker1985] Calcium absorption and achlorhydria (1985). https://pubmed.ncbi.nlm.nih.gov/4000241/ DOI: 10.1056/NEJM198507113130202
Complete structured claim and evidence
In 14 healthy volunteers, omeprazole-induced anacidity slightly reduced release of orally administered labeled liver cobalamins in gastric aspirates at 5 and 30 minutes versus placebo.
Omeprazole → Gastric release of food-bound cobalamin source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Double-blind crossover in 14 healthy humans using 57Co-labeled rabbit liver
exposure
Short-term omeprazole versus placebo; dose not in inspected abstract
limitations
Short-term food tracer experiment, not a long-term deficiency outcome.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Suppressing acid delayed early stomach release in this experiment.
primary_references
[kittang-1987-anacidity] Effect of gastric anacidity on the release of cobalamins from food and their subsequent binding to R-protein. (1987). https://pubmed.ncbi.nlm.nih.gov/3423731/ DOI: 10.3109/00365528708991952
tissue_or_cell_type
Stomach lumen
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 127–138
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind crossover in 14 healthy humans using 57Co-labeled rabbit liver · source_derived_draft · unverified_draft
### b12-abs-anacidity-gastric In 14 healthy volunteers, omeprazole-induced anacidity slightly reduced release of orally administered labeled liver cobalamins in gastric aspirates at 5 and 30 minutes versus placebo. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Suppressing acid delayed early stomach release in this experiment. organism: Homo sapiens tissue_or_cell_type: Stomach lumen experimental_model: Double-blind crossover in 14 healthy humans using 57Co-labeled rabbit liver limitations: Short-term food tracer experiment, not a long-term deficiency outcome. exposure: Short-term omeprazole versus placebo; dose not in inspected abstract cross_nutrient: false [kittang-1987-anacidity] Effect of gastric anacidity on the release of cobalamins from food and their subsequent binding to R-protein. (1987). https://pubmed.ncbi.nlm.nih.gov/3423731/ DOI: 10.3109/00365528708991952
Complete structured claim and evidence
In the same crossover experiment, jejunal release of labeled liver cobalamins was near 90% after either omeprazole or placebo, despite earlier gastric effects.
Omeprazole → Jejunal release of food-bound cobalamin source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Double-blind crossover in 14 healthy humans using 57Co-labeled rabbit liver
exposure
Short-term omeprazole versus placebo
limitations
Luminal release is not systemic absorption; this observation cannot exclude long-term effects on status.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Most liver-bound B12 was still released by the jejunum.
primary_references
[kittang-1987-anacidity] Effect of gastric anacidity on the release of cobalamins from food and their subsequent binding to R-protein. (1987). https://pubmed.ncbi.nlm.nih.gov/3423731/ DOI: 10.3109/00365528708991952
tissue_or_cell_type
Upper jejunal lumen
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 140–151
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind crossover in 14 healthy humans using 57Co-labeled rabbit liver · source_derived_draft · unverified_draft
### b12-abs-anacidity-jejunum In the same crossover experiment, jejunal release of labeled liver cobalamins was near 90% after either omeprazole or placebo, despite earlier gastric effects. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Most liver-bound B12 was still released by the jejunum. organism: Homo sapiens tissue_or_cell_type: Upper jejunal lumen experimental_model: Double-blind crossover in 14 healthy humans using 57Co-labeled rabbit liver limitations: Luminal release is not systemic absorption; this observation cannot exclude long-term effects on status. exposure: Short-term omeprazole versus placebo cross_nutrient: false [kittang-1987-anacidity] Effect of gastric anacidity on the release of cobalamins from food and their subsequent binding to R-protein. (1987). https://pubmed.ncbi.nlm.nih.gov/3423731/ DOI: 10.3109/00365528708991952
Complete structured claim and evidence
The same KCl run-in modestly lowered mean bicarbonate from 24.5 to 23.7 mmol/L and increased chloride; urinary ammonium did not increase.
Potassium chloride → Plasma bicarbonate concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Potassium salt/chloride -> acid-base balance.
experimental_model
Same two-week CKD cohort.
limitations
No randomized comparator; no significant blood-pressure or eGFR change.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Homo sapiens
plain_language
The chloride salt affected acid-base measurements as well as potassium.
primary_references
[k-gritter2022] Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD (2022). https://pubmed.ncbi.nlm.nih.gov/35609996/ DOI: 10.1681/asn.2022020147
tissue_or_cell_type
Plasma and urine
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1650–1660
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same two-week CKD cohort. · source_derived_draft · unverified_draft
### k-ckd-kcl-bicarbonate-response The same KCl run-in modestly lowered mean bicarbonate from 24.5 to 23.7 mmol/L and increased chloride; urinary ammonium did not increase. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chloride salt affected acid-base measurements as well as potassium. organism: Homo sapiens tissue_or_cell_type: Plasma and urine experimental_model: Same two-week CKD cohort. limitations: No randomized comparator; no significant blood-pressure or eGFR change. cross_nutrient: Potassium salt/chloride -> acid-base balance. [k-gritter2022] Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD (2022). https://pubmed.ncbi.nlm.nih.gov/35609996/ DOI: 10.1681/asn.2022020147
Complete structured claim and evidence
Two weeks of KCl raised mean plasma potassium from 4.3 to 4.7 mmol/L; 21 of 191 CKD participants developed hyperkalemia.
Potassium chloride → Plasma potassium concentration source_derived_draftungraded
Experimental context and source evidence
experimental_model
Uncontrolled run-in; CKD G3b-4.
exposure
40 mmol/day KCl; 83% used RAAS inhibitors.
limitations
11% is this cohort rate, not general-population risk or a dose recommendation.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Homo sapiens
plain_language
Reduced kidney clearance changes the response to an added potassium load.
primary_references
[k-gritter2022] Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD (2022). https://pubmed.ncbi.nlm.nih.gov/35609996/ DOI: 10.1681/asn.2022020147
tissue_or_cell_type
Plasma
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1638–1648
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Uncontrolled run-in; CKD G3b-4. · source_derived_draft · unverified_draft
### k-ckd-kcl-plasma-rise Two weeks of KCl raised mean plasma potassium from 4.3 to 4.7 mmol/L; 21 of 191 CKD participants developed hyperkalemia. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced kidney clearance changes the response to an added potassium load. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Uncontrolled run-in; CKD G3b-4. limitations: 11% is this cohort rate, not general-population risk or a dose recommendation. exposure: 40 mmol/day KCl; 83% used RAAS inhibitors. [k-gritter2022] Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD (2022). https://pubmed.ncbi.nlm.nih.gov/35609996/ DOI: 10.1681/asn.2022020147
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Intestinal chloride loss from defective DRA

Condition: machinery_impairment · Pathogenic SLC26A3 variants.

Normal role: DRA supports intestinal chloride/bicarbonate exchange.

Recorded consequence: Chloride-rich diarrhea and persistent intestinal salt loss.

Scope: Human congenital chloride diarrhea; genetic machinery defect.

Basolateral exchanger failure stops gastric acid secretion

Condition: machinery_impairment · Slc4a2 deletion.

Normal role: AE2 exchanges bicarbonate and chloride at the parietal-cell basolateral membrane.

Recorded consequence: Achlorhydria and abnormal secretory membranes.

Scope: Mouse genetic deletion.

Another gastric chloride pathway is lost

Condition: machinery_impairment · Slc26a9 deletion.

Normal role: Slc26a9 contributes to parietal-cell anion handling.

Recorded consequence: Acid secretion and tubulovesicles were lost.

Scope: Mouse stomach; not a human dietary deficiency.

Impaired chloride extrusion changes GABA responses

Condition: machinery_impairment · Antisense reduction of KCC2.

Normal role: KCC2 helps maintain neuronal chloride gradients.

Recorded consequence: GABA response reversal potential shifted positively.

Scope: Rat neurons; transporter manipulation, not a dietary shortage.

A muscle chloride-channel defect causes stiffness

Condition: machinery_impairment · Inherited CLCN1 defects.

Normal role: ClC-1 contributes to muscle electrical stability.

Recorded consequence: Membrane hyperexcitability and myotonia.

Scope: Human genetic channelopathy; not proof of low chloride intake.

Chloride/bicarbonate exchange fails in the collecting duct

Condition: machinery_impairment · Slc26a4 deletion.

Normal role: Pendrin supports apical chloride/bicarbonate exchange and bicarbonate secretion.

Recorded consequence: Reduced exchange, more acidic urine and higher blood bicarbonate.

Scope: Mouse kidney; genetic machinery impairment.

A chloride/proton exchanger defect disrupts nutrient retrieval

Condition: machinery_impairment · Clcn5 disruption.

Normal role: Proximal-tubule endocytosis retrieves filtered proteins and associated molecules.

Recorded consequence: Impaired endocytosis and urinary loss of vitamin D precursor.

Scope: Mouse Dent disease model; not insufficient dietary chloride.

Chloride machinery is needed to dissolve bone mineral

Condition: machinery_impairment · Clcn7 loss.

Normal role: Osteoclasts acidify a sealed resorption compartment.

Recorded consequence: Failed lacunar acidification and bone resorption.

Scope: Mouse knockout with related human genetic evidence.

Severely chloride-deficient infant formula

Condition: nutrient_deficiency · Manufacturing-related low chloride intake.

Normal role: Adequate dietary chloride supports electrolyte and acid–base balance.

Recorded consequence: Hypochloremic alkalosis, poor growth and hormonal activation.

Scope: Historical infants exclusively receiving deficient formula.

Chloride loss maintains alkalosis

Condition: nutrient_deficiency · Furosemide-induced chloride depletion maintained by NaCl restriction.

Normal role: Renal bicarbonate disposal depends on electrolyte context.

Recorded consequence: KCl corrected alkalosis despite persistent low plasma volume and filtration.

Scope: Controlled human loss/repletion experiment, not isolated low dietary intake.

Low duct permeability leaves more salt in sweat

Condition: machinery_impairment · Cystic-fibrosis-associated low chloride permeability.

Normal role: Sweat ducts reabsorb part of their secreted NaCl.

Recorded consequence: Poor NaCl reabsorption and high sweat salt.

Scope: Human isolated sweat ducts; genetic transport disease.

Kidney chloride-channel failure wastes salt

Condition: machinery_impairment · Pathogenic CLCNKB variants.

Normal role: ClC-Kb supports renal chloride reabsorption.

Recorded consequence: Salt wasting, hypokalemia and metabolic alkalosis.

Scope: Human Bartter type III; genetic machinery impairment.

A basolateral channel defect changes drug response

Condition: machinery_impairment · Clcnk2 deletion.

Normal role: Basolateral chloride exit supports nephron salt transport.

Recorded consequence: Salt wasting and altered diuretic response.

Scope: Mouse knockout.

Low blood chloride and poor diuretic response

Condition: biomarker_context · Measured hypochloremia in treated heart failure.

Normal role: Renal salt handling integrates chloride and neurohormonal signals.

Recorded consequence: Association with poor diuretic response.

Scope: Human cohort; biomarker is not proof of dietary shortage.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Calcium: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Which chloride intake or blood measurement predicts a specific intracellular chloride gradient?These gradients are transporter- and tissue-dependent; no universal conversion is established by these studies.
Does correcting hypochloremia improve outcomes in heart failure?The cohort and ten-person pilot do not establish efficacy or a treatment strategy.
Which component of balanced versus saline fluids accounts for a clinical effect?Multiple solutes differ; SMART and PLUS use different primary endpoints, so these findings cannot establish an isolated chloride mechanism or a simple contradiction.
How much do airway cell type and inflammatory state determine pendrin versus CFTR contribution?Calu-3 and IL-4-treated primary surface epithelia are different systems; preserved context explains why they need not disagree.
Does dietary chloride limitation impair absorption of calcium, iron or food-bound B12 in otherwise healthy humans?Transporter knockout and acid-suppression findings do not establish this dietary causal chain. Meal effects and downstream release can compensate.
How does ClC-5 dysfunction balance urinary vitamin D precursor loss against PTH-driven activation?The original study proposes opposing downstream effects; calcium and phosphate outcomes cannot be predicted from a single isolated arrow.
How do direct potassium sensing, chloride sensing and osmotic regulation combine in each native nephron segment?Purified kinase sites and cell-voltage pathways coexist; their quantitative contribution cannot be inferred by joining experiments.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Chloride

The mechanisms

Chloride bound the WNK1 catalytic region and stabilized its inactive conformation.

Chloride inhibited WNK1 autophosphorylation; binding-site mutations reduced this inhibition.

Phosphorylated CFTR channels opened with ATP but not Mg-free ATP in this preparation.

Pendrin-null collecting ducts had reduced apical chloride/bicarbonate exchange and impaired bicarbonate secretion.

Oral KCl corrected induced chloride-depletion alkalosis while plasma volume, body weight and filtration remained reduced.

Chloride binding increased catalytic rates and altered pH dependence of the human pancreatic amylase variant.

The Clcn5-null model lost 25-hydroxyvitamin D3 in urine.

Developmental KCC2 expression accompanied the shift toward hyperpolarizing GABA-A responses.

Clcn7-null osteoclasts failed to acidify the resorption lacuna.

Myeloperoxidase used hydrogen peroxide to oxidize chloride to hypochlorous acid.

A seven-month-old infant fed chloride-deficient formula developed hypochloremic alkalosis.

Saline produced sustained hyperchloremia, unlike Plasma-Lyte 148.

DRA variants segregated with congenital chloride diarrhea in the studied families.

AE2-null mice failed to secrete gastric acid.

AE2-null parietal cells had poorly developed secretory canaliculi and few tubulovesicles.

Slc26a9-null mice lost gastric acid secretion at five weeks.

Slc26a9 deletion eliminated parietal-cell tubulovesicles and shifted H-K-ATPase localization to the apical pole.

CFTR pore-region mutations changed anion selectivity, demonstrating that CFTR forms an anion channel.

PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal.

Lower intracellular chloride activated the WNK1–OSR1/SPAK pathway in the pancreatic experiments.

WNK1-mediated OSR1/SPAK activation increased CFTR bicarbonate permeability.

OSR1/SPAK activation inhibited CFTR-dependent chloride/bicarbonate exchange in the tested system.

Cryo-EM resolved bicarbonate-bound human AE1 and identified substrate-recognition features.

Chloride opposed osmolyte-stimulated WNK1 autophosphorylation.

Chloride also opposed osmolyte-stimulated WNK3 autophosphorylation.

WNK1 E388 mutations reduced potassium inhibition while retaining kinase activity.

Mutation of the corresponding WNK3 E314 site reduced potassium inhibition.

Suppressing KCC2 shifted the GABA-A reversal potential in a positive direction in mature neurons.

Nkcc1 deletion attenuated GABA-triggered depolarization and calcium transients during early hippocampal development.

Nkcc1-null immature retinal neurons retained approximately 30 mM intracellular chloride, similar to controls.

SERT Asn101 experiments linked chloride binding to concentrative serotonin uptake.

CLCN1 linkage and a disease-associated substitution implicated the muscle chloride channel in inherited myotonia.

Deleting LRRC8A abolished VRAC currents; reconstitution required LRRC8A with another LRRC8 isoform.

Regulatory cell-volume decrease depended on LRRC8 proteins.

Taurine flux depended on LRRC8 proteins in the tested cells.

Serum bicarbonate was 27.4 versus 24 meq/L in pendrin-null and control mice.

Slc4a8 deletion abolished the thiazide-sensitive NaCl absorption measured in cortical collecting ducts.

Isolated-duct results supported parallel pendrin and NDCBE action in electroneutral NaCl absorption.

Adding luminal choline chloride or RbCl reduced renin release, whereas the tested sodium salts without chloride did not.

Luminal bumetanide increased renin release during high-NaCl perfusion, supporting cotransporter-dependent sensing.

Chloride binding influenced E233 positioning and the structural region that orients D300 in pancreatic amylase.

Myeloperoxidase favored thiocyanate kinetically and generated hypothiocyanite despite 100 mM chloride.

ClC-5 transported protons against their electrochemical gradient in coupling with anion transport.

ClC-4 also supported secondary active proton transport in the expression assay.

Measured ClC-5 transport stoichiometry was two chloride ions per proton.

Clcn5 deletion reduced both receptor-mediated and fluid-phase proximal-tubule endocytosis.

Tubular endocytosis of PTH was reduced in the Clcn5-null model.

NaPi-2 redistributed toward intracellular vesicles at steady state despite slower internalization.

NHE3 also redistributed toward intracellular vesicles at steady state despite slower internalization.

Tail-current reversal potentials supported two chloride ions exchanged per proton by ClC-7/Ostm1.

Both the amino-terminal and transmembrane regions of Ostm1 were required for the measured ClC-7 exchange activity.

Clcn7-null mice had severe osteopetrosis despite normal osteoclast numbers.

Hyperreninemia and hyperaldosteronism accompanied the deficient-formula case and normalized after adequate feeding.

Both infants resumed normal weight gain after switching to a formula with adequate chloride.

Urinary bicarbonate excretion increased during correction of chloride-depletion alkalosis.

The same KCl load did not change acid–base status in sodium-depleted subjects who were not chloride-depleted.

CF sweat ducts showed low chloride permeability and impaired NaCl reabsorption.

CLCNKB loss-of-function variants caused renal salt-wasting hypokalemic alkalosis in the studied families.

Affected CLCNKB families had hypokalemia alongside salt wasting.

Knockout patch-clamp studies identified ClC-K2 as a major basolateral chloride channel in the tested nephron segments.

ClC-K2-null mice lacked the usual furosemide natriuretic response and had a severely blunted thiazide response.

Hypochloremia was associated with poor diuretic response in the heart-failure cohort.

The pilot reported a mean serum chloride rise of 2.2 mmol/L after sodium-free lysine chloride supplementation.

The fall in strong-ion difference was greater after saline than Plasma-Lyte.

Renal cortical perfusion fell from baseline after saline but not Plasma-Lyte.

MAKE30 occurred in 14.3% with balanced crystalloids versus 15.4% with saline (P=0.04).

Ninety-day mortality was 21.8% versus 22.0% with balanced fluid and saline (P=0.90).

New renal-replacement therapy occurred in 12.7% versus 12.9%; the difference confidence interval included zero.

Pendrin knockdown did not change measured Calu-3 bicarbonate secretion.

IL-4-induced pendrin supported chloride/bicarbonate exchange in primary airway surface cultures.

Inducing pendrin approximately doubled the forskolin-stimulated CFTR-sensitive current in the tested cells.

Low-K medium lowered intracellular chloride in HEK293 and mDCT cells; depolarizing Kir4.1 mutants increased it.

Increasing chloride inhibited recombinant WNK4 phosphorylation of SPAK more strongly than WNK1/3 in matched assays.

Catalytically active WNK4 phosphorylated and activated SPAK in biochemical assays.

SPAK phosphorylated human NCC at Thr46, Thr55 and Thr60; Thr60 mutation impaired chloride-depletion-induced NCC activation.

OSR1 phosphorylated human NCC at Thr46, Thr55 and Thr60; Thr60 mutation impaired chloride-depletion-induced NCC activation.

Low-potassium feeding on high salt reduced sodium excretion; NCC deletion blunted the blood-pressure response.

Cloned renal NKCC2 supported bumetanide-sensitive sodium-potassium-chloride cotransport in oocytes, distinct from NCC potassium-independent NaCl transport.